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Brain magnetic resonance imaging in acute optic neuritis. Experience of the Optic Neuritis Study Group.

OBJECTIVE: Changes in the brain on magnetic resonance images are common in patients with optic neuritis even when there is no other clinical evidence of multiple sclerosis. The current study was designed to determine systematically the prevalence of brain abnormalities on magnetic resonance images in the patients entered into the Optic Neuritis Treatment Trial. DESIGN: Prospective multicenter clinical trial. SETTING: Referral centers. PATIENTS AND METHODS: Brain magnetic resonance images from 418 patients with acute optic neuritis (77% women; mean age, 32.0 years) were evaluated at a central reading center with the use of a standardized classification system (ranging from 0 for normal to IV for most extensive changes). RESULTS: Of the scans, 40.9% were classified as grade 0, 10.8% as grade I, 9.1% as grade II, 6.7% as grade III, and 32.5% as grade IV. For patients with isolated (monosymptomatic) optic neuritis, 26.7% had two or more lesions. CONCLUSIONS: We found a lower prevalence of brain magnetic resonance imaging abnormalities in isolated optic neuritis than previous studies have reported. This likely is due to our study having a higher degree of standardization of patient inclusion criteria, which limited patient selection bias.

Acute Disease↗

Combined imaging and chemical sensing of fertilization-induced acid release from single sea urchin eggs.

We demonstrate a microarray sensor capable of obtaining both chemical and visual information on multiple cells simultaneously with single-cell resolution. The array was fabricated by covalently immobilizing a thin, pH-sensitive polymer layer on the distal end of an optical imaging fiber. The sensor's ability to measure localized chemical dynamics in real-time was evaluated using sea urchin fertilization biochemistry as a model system. Following sea urchin fertilization, the Na(+)/H(+) transporter is activated to exchange extracellular sodium ions for intracellular hydrogen ions, causing a release of hydrogen ions at the egg's surface. By placing the pH sensor proximal to the egg and switching between a fluorescence image and a white light image, we were able to observe both localized pH changes following fertilization as well as morphological transformations during cell division.

Animals↗

Magnetization transfer and diffusion tensor MR imaging of the optic radiations and calcarine cortex from patients with Leber's hereditary optic neuropathy.

Optic nerve abnormalities are easily detectable in patients with Leber's hereditary optic neuropathy (LHON), using magnetic resonance imaging (MRI). However, the presence of structural changes in the optic radiations and calcarine cortex of these patients is still an unresolved issue. In this study, we obtained magnetization transfer (MT) and diffusion tensor (DT) MRI to investigate the integrity of these structures in patients with LHON. Dual echo, MT- and DT-MRI scans of the brain were obtained from 10 men with LHON and 10 healthy sex- and age-matched controls. After image co-registration, we obtained MT ratio (MTR), average diffusivity (D) and fractional anisotropy (FA) maps. MTR, D and FA values for the white matter of the optic radiations and MTR and D values for the calcarine cortex were obtained using a region of interest (ROI) analysis. No macroscopic abnormalities were detected in any of the scans from LHON patients and controls. No statistically significant differences of MTR, D or FA values were found for any of the regions studied in LHON patients and healthy controls. Our results suggest that, in patients with LHON, the optic radiations and the calcarine cortex are spared from structural damage, both at a macroscopic and a microscopic level.

Adult↗

Functional imaging of the embryonic pacemaking and cardiac conduction system over the past 150 years: technologies to overcome the challenges.

Early analyses of cardiac pacemaking and conduction system (CPCS) development relied on classic histology and visual inspection of the beating heart. Current techniques that facilitate delineation of the CPCS include the use of specific antibody markers and transgenic mouse lines specifically expressing reporter genes. Assaying the function of tiny embryonic hearts required an increase in the level of spatial and temporal resolution. Current methods for such analyses include the use of intracellular and extracellular microelectrodes, echocardiography, rapid optical imaging using fluorescent dyes, and most recently optical coherence tomography. This review will focus on methods developed to investigate the functional emergence of the embryonic cardiac conduction system. Where appropriate, the methods used to delineate the anatomic pathways will also be discussed. The combination of techniques to capture both morphological and functional data from the CPCS will further improve with continued interdisciplinary collaboration. The Supplementary Material referred to in this article can be found at the Anatomical Record website (http://www.interscience.wiley.com/jpages/0003-276X/suppmat).

Action Potentials↗

Influence of cataract on optical coherence tomography image quality and retinal thickness.

BACKGROUND: As optical coherence tomography (OCT) is widely used for diagnosis and monitoring of ocular pathology, especially in the elderly people, the influence of cataract on image quality and macular retinal thickness was studied. METHODS: In 29 patients scheduled for cataract surgery, preoperative and postoperative OCT scans were obtained. Cataracts were categorised as nuclear, posterior or cortical. Parameters for image quality (signal-to-noise ratio (SNR)) and signal strength and macular thickness were compared. A three-level expert grading scale was used to evaluate the discriminative abilities of SNR and signal strength. RESULTS: Nuclear cataracts (n = 12) provided better preoperative scans (higher SNR/signal strength) than posterior (n = 7) and cortical (n = 10) cataracts (p<0.004). Postoperatively SNR and signal strength increased significantly in all patients (p<0.001). The SNR was better at discriminating poor from acceptable and good scans than signal strength (area under the receiver operating curve: 0.879 and 0.810, respectively). Postoperative macular thickness overall showed a significant increase (p = 0.005), most evident in patients with posterior cataracts (p = 0.028). CONCLUSIONS: OCT imaging is influenced by cataract; image quality is reduced preoperatively and macular thickness measurements are slightly increased postoperatively. In individual patients, OCT scans remain reliable for gross clinical interpretation, even in the presence of cataract.

Aged↗

Chemical micropatterning of polycarbonate for site-specific peptide immobilization and biomolecular interactions.

Polycarbonate (PC) is a useful substrate for the preparation of microfluidic devices. Recently, its utility in bioanalysis has attracted much attention owing to the possibility of using compact discs as platforms for the high-throughput analysis of biomolecular interactions. In this article we report a novel method for the chemical micropatterning of polycarbonate based on the printing of functionalized silica nanoparticles. The semicarbazide groups present on the surface of the nanoparticles were used for the site-specific semicarbazone ligation of unprotected peptides derivatized by an alpha-oxoaldehyde group. The peptide micropatterns permitted the specific capture of antibodies. We report also the characterization of micropatterns on PC by using a wide-field optical imaging technique called Sarfus; this allows the detection of nm-thick films by using nonreflecting PC substrates and an optical microscope working with reflected differential interference contrast. The method described here is an easy way to modify polycarbonate surfaces for biomolecular interaction studies and should stimulate the use of PC for developing plastic biosensors.

Enzymes, Immobilized↗

Landcover classification in MRF context using Dempster-Shafer fusion for multisensor imagery.

This work deals with multisensor data fusion to obtain landcover classification. The role of feature-level fusion using the Dempster-Shafer rule and that of data-level fusion in the MRF context is studied in this paper to obtain an optimally segmented image. Subsequently, segments are validated and classification accuracy for the test data is evaluated. Two examples of data fusion of optical images and a synthetic aperture radar image are presented, each set having been acquired on different dates. Classification accuracies of the technique proposed are compared with those of some recent techniques in literature for the same image data.

Algorithms↗

Spatial variations in optical and physiological properties of healthy breast tissue.

Near-infrared (NIR) diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration (FDPM) instrument. Wavelength-dependent absorption and reduced scattering parameters (micro(a) and micro(s'), respectively) were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy-(HbO(2)) and deoxy-(Hb-R) hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal (PRE) women (20 to 30 microM) is approximately two-fold higher than for postmenopausal (POST) subjects at all positions. POST women have approximately 50% higher lipid content (50 to 60%) than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects (30 to 40%) than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration (THC), 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale (3 cm) changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for micro(a) and 5 to 12% for micro(s'). Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering (674 nm) within an individual.

Adolescent↗

Photon-limited synthetic-aperture imaging for planet surface studies.

The carrier-to-noise ratio that results from phase-sensitive heterodyne detection in a photon-limited synthetic-aperture ladar (SAL) is developed, propagated through synthetic-aperture signal processing, and combined with speckle to give the signal-to-noise ratio of the resultant image. Carrier- and signal-to-noise ratios are defined in such a way as to be familiar to the optical imaging community. Design equations are presented to show that a 10-microm SAL in orbit around Mars can give centimeter-class resolution with reasonable laser power. SAL is harder to implement in the short-wave infrared and is probably not practical at visible wavelengths unless many separate images can be averaged. Some tutorial information on phase-sensitive heterodyne detection and on synthetic-aperture signal processing and image formation is provided.

Journal Article↗

Linear and nonlinear reconstruction for optical tomography of phantoms with nonscattering regions.

Most research in optical imaging incorrectly assumes that light transport in nonscattering regions in the head may be modeled by use of the diffusion approximation. The effect of this assumption is examined in a series of experiments on tissue-equivalent phantoms. Images from cylindrical and head-shaped phantoms with and without clear regions [simulating the cerebrospinal fluid (CSF) filled ventricles] and a clear layer (simulating the CSF layer surrounding the brain) are reconstructed with linear and nonlinear reconstruction techniques. The results suggest that absorbing and scattering perturbations can be identified reliably with nonlinear reconstruction methods when the clear regions are also present in the reference data but that the quality of the image degrades considerably if the reference data does not contain these features. Linear reconstruction performs similarly to nonlinear reconstruction, provided the clear regions are present in the reference data, but otherwise linear reconstruction fails. This study supports the use of linear reconstruction for dynamic imaging but suggests that, in all cases, image quality is likely to improve if the clear regions are modeled correctly.

Algorithms↗

Effects of background fluorescence in fluorescence molecular tomography.

Recent advances in optical imaging systems and systemically administered fluorescent probes have significantly improved the ways by which we can visualize proteomics in vivo. A key component in the design of fluorescent probes is a favorable biodistribution, i.e., localization only in the targeted diseased tissue, in order to achieve high contrast and good detection characteristics. In practice, however, there is always some level of background fluorescence present that could result in distorted or obscured visualization and quantification of measured signals. In this study we observe the effects of background fluorescence in tomographic imaging. We demonstrate that increasing levels of background fluorescence result in artifacts when using a linear perturbation algorithm, along with a significant loss of image fidelity and quantification accuracy. To correct for effects of background fluorescence, we have applied cubic polynomial fits to bulk raw measurements obtained from spatially homogeneous and heterogeneous phantoms. We show that subtraction of the average fluorescence response from the raw data before reconstruction can improve image quality and quantification accuracy as shown in relatively homogeneous or heterogeneous phantoms. Subtraction methods thus appear to be a promising route for adaptively correcting nonspecific background fluorochrome distribution.

Algorithms↗

Adaptive autofocusing: a closed-loop perspective.

We present an adaptive autofocusing scheme. In this scheme, the focus measure is updated with focus tuning. To achieve this, we construct the focus measure by using image moments and develop an adaptive focus-tuning strategy to estimate the measure in closed loop. It is shown that the adaptive updating of the focus measure enables us to overcome the dependence of autofocusing on the image contents. Such an adaptive closed-loop focusing operation also effectively suppresses both the effect of the noise in optical imaging and the effect of time delay due to image processing time. Therefore a high accuracy of autofocusing is guaranteed. The effectiveness of the proposed scheme is demonstrated by simulations and experiments.

Algorithms↗

[Development of a universal interface for the exchange of medical image data using magneto-optical media].

Digital images generated by medical imaging form the basis for radiological diagnosis and surgical planning. Despite the advent of the DICOM 3.0 standard for medical image communication, widespread application of the existing information is often limited by incompatibility of the data formatting used by different equipment generations, and the manufacturer-specific standards employed. An exchange interface based on magneto optical discs has been developed to retrieve and present medical image data regardless of the technological hardware and the specific formats used. Specially adapted routines to retrieve the data first had to be developed. A modular program structure was used to allow flexibility in the implementation of further routines and other exchange media. Over 20,000 CT and MRI images including header information obtained from different General Electric and Siemens scanners were extracted successfully from MO discs. The image data were used for follow up and surgical planning and were transferred to a PAC-server. The interface proved reliable and easy to use. Support for further proprietary formats is currently being developed. The present exchange interface permits reliable retrieval of digital images for diagnostic and surgical planning purposes, regardless of the hardware generation and manufacturer-specific formats.

Computers↗

Real-time three-dimensional ultrasound for guiding surgical tasks.

OBJECTIVE: As a stand-alone imaging modality, two-dimensional (2D) ultrasound (US) can only guide basic interventional tasks due to the limited spatial orientation information contained in these images. High-resolution real-time three-dimensional (3D) US can potentially overcome this limitation, thereby expanding the applications for US-guided procedures to include intracardiac surgery and fetal surgery, while potentially improving results of solid organ interventions such as image-guided breast, liver or prostate procedures. The following study examines the benefits of real-time 3D US for performing both basic and complex image-guided surgical tasks. MATERIALS AND METHODS: Seven surgical trainees performed three tasks in an acoustic testing tank simulating an image-guided surgical environment using 2D US, biplanar 2D US, and 3D US for guidance. Surgeon-controlled US imaging was also tested. The evaluation tasks were (1) bead-in-hole navigation; (2) bead-to-bead navigation; and (3) clip fixation. Performance measures included completion time, tool tip trajectory, and error rates, with endoscope-guided performance serving as a gold-standard reference measure for each subject. RESULTS: Compared to 2D US guidance, completion times decreased significantly with 3D US for both bead-in-hole navigation (50%, p = 0.046) and bead-to-bead navigation (77%, p = 0.009). Furthermore, tool-tip tracking for bead-to-bead navigation demonstrated improved navigational accuracy using 3D US versus 2D US (46%, p = 0.040). Biplanar 2D imaging and surgeon-controlled 2D US did not significantly improve performance as compared to conventional 2D US. In real-time 3D mode, surgeon-controlled imaging and changes in 3D image presentation made by adjusting the perspective of the 3D image did not diminish performance. For clip fixation, completion times proved excessive with 2D US guidance (> 240 s). However, with real-time 3D US imaging, completion times and error rates were comparable to endoscope-guided performance. CONCLUSIONS: Real-time 3D US can guide basic surgical tasks more efficiently and accurately than 2D US imaging. Real-time 3D US can also guide more complex surgical tasks which may prove useful for procedures where optical imaging is suboptimal, as in fetal surgery or intracardiac interventions.

Humans↗

Molecular imaging and cancer.

Molecular imaging is a relatively new discipline, which developed over the past decade, initially driven by in situ reporter imaging technology. Noninvasive in vivo molecular imaging developed more recently and is based on magnetic resonance and nuclear (positron emission tomography; gamma camera) and in vivo optical imaging systems. Molecular imaging has its roots in both molecular biology and cell biology, as well as imaging technology. Most current in vivo molecular imaging strategies are "indirect" and involve the coupling of a "reporter/marker gene" with a complimentary "reporter/marker probe." Imaging the level of probe accumulation provides indirect information related to the level of reporter gene expression. Reporter gene constructs are driven by upstream promoter/enhancer elements that function as an "on/off switch"; they can be constitutive, leading to continuous transcription to identify the site and monitor the level and duration of gene (vector) activity. Alternatively, they can be inducible, leading to controlled gene expression, or they can function as a sensor element to monitor the level of endogenous promoters and transcription factors. Three indirect strategies for imaging therapeutic transgenes are discussed. Several examples of imaging endogenous biological processes in animals using reporter constructs, radiolabeled probes, and positron emission tomography imaging are reviewed (p53-dependent gene expression, T-cell receptor-dependent activation of T-lymphocytes, and trafficking of T-lymphocytes). Issues related to the translation of noninvasive molecular imaging technology into the clinic are discussed.

Animals↗

Assessment of coronary arterial thrombus by optical coherence tomography.

We analyzed optical coherence tomographic (OCT) characteristics of different types of coronary thrombi that had been confirmed at postmortem histologic examination. We examined 108 coronary arterial segments of 40 consecutive human cadavers. OCT images of red and white thrombi were obtained and the intensity property of these thrombi was analyzed. Red and white thrombi were found in 16 (17%) and 19 (18%) of the 108 arterial segments, respectively. Red thrombi were identified as high-backscattering protrusions inside the lumen of the artery, with signal-free shadowing in the OCT image. White thrombi were identified as low-backscattering projections in the OCT image. There were no significant differences in peak intensity of OCT signal between red and white thrombi (130+/-18 vs 145+/-34, p=0.12). However, the 1/2 attenuation width of the signal intensity curve, which was defined as the distance from peak intensity to its 1/2 intensity, was significantly different between red and white thrombi (324+/-50 vs 183+/- 42 microm, p<0.0001). A cut-off value of 250 microm in the 1/2 width of signal intensity attenuation can differentiate white from red thrombi with a sensitivity of 90% and specificity of 88%. We present the first detailed description of the characteristics of different types of coronary thrombi in OCT images. Optical coherence tomography may allow us not only to estimate plaque morphology but also to distinguish red from white thrombi.

Aged↗

Microimaging.

Recent technological advances in optics, imaging, and illumination have brought forth a new generation of miniature laparoscopes suitable for emergency laparoscopy. A simple comparative analysis was conducted to determine which optic would be most suitable in an emergent environment. Animal experiments were designed to emulate a videolaparoscopic procedure. Six telescopes were visually assessed as to sharpness, depth of field, brightness and displayed image size on the TV monitor. A videotape record was obtained. Two telescopes were perceived as clearly superior in the field. When they meet image specification, miniature laparoscopes can be useful in the emergency setting.

Journal Article↗

Use of intrinsic optical signals to monitor physiological changes in brain tissue slices.

Optical imaging techniques have the potential to bring a combination of high spatial and temporal resolution to studies of brain function. Many optical techniques require the addition of a dye or fluorescent marker to the tissue, and such methods have proven extremely valuable. It is also known that the intrinsic optical properties of neural tissue are affected by certain physiological changes and that these intrinsic optical signals can provide information not available by other means. Most authors attribute the intrinsic optical change to alterations in cell volume and concomitant change in the concentration of the cytosol. In this article we review the literature on intrinsic optical signals, covering both the mechanisms of the optical change and its use in various branches of neurophysiology. We also discuss technical aspects of the technique as used with hippocampal slices, including illumination methods, cameras, experimental methods, and data collection and analysis procedures. Finally we present data from investigations in which we used intrinsic optical signals in hippocampal slices to study the extent of spread of synaptic activation, propagation of spreading depression, extent and severity of the response to hypoxia, and tissue response to osmotic challenges. We conclude that (1) at least two processes generate intrinsic optical signals in hippocampal slices, one of which causes light scattering to change inversely with cell volume and is related to dilution of the cytoplasm, while the other, opposite in sign, may be due to mitochondrial swelling; and (2) the intrinsic optical signal can be a useful tool for spatial mapping of relatively slow events, but is not suitable for study of fast physiological processes.

Animals↗