Magnetic resonance imaging of optic neuritis in a patient with systemic lupus erythematosus.
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Adult↗
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Results for “Optical imaging”
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Imaging of in vitro chicken leg using time-resolved near-infrared optical tomography.
Near-infrared optical imaging gains much attention because of its noninvasiveness and deep penetration depths into tissue. Here, we report near-infrared optical tomographic imaging of an in vitro chicken leg from time-resolved measurements. The in vitro chicken leg, dipped in a cylindrical container filled with diluted Intralipid-10% solution, was imaged with a multichannel time-resolved imaging system. A two-dimensional reconstruction algorithm based on a modified generalized pulse spectrum technique has been developed to reconstruct the images of both the absorption and reduced scattering coefficients simultaneously and quickly. The results demonstrate that a simultaneous reconstruction of absorption and reduced scattering coefficients from time-resolved measurement has a potential to reveal the changes in the optical properties associated with not only the physiological information but also the anatomical structure of the organ.
Algorithms↗
Molecular imaging in drug discovery and development: potential and limitations of nonnuclear methods.
Noninvasive conventional imaging methods are established technologies in modern drug discovery and development providing valuable morphological, physiological, and metabolic information to characterize disease phenotypes, to evaluate the efficacy of therapy and to identify and develop potential biomarkers for clinical drug evaluation. The development of target-specific or molecular imaging has added a new dimension: molecular events such as the target expression, the drug-target interaction, or the activation of signal transduction pathways can be studied in the intact organism with high spatial and temporal resolution. Molecular imaging is inherently a multimodality approach. In this article, we review the role of molecular imaging for drug discovery and development focusing on nonnuclear imaging methods, i.e., magnetic resonance imaging (MRI) and optical imaging techniques based on fluorescence and bioluminescence readouts. Examples discussed are direct visualization of target expression using target-specific ligands or reporter genes, pathway imaging, and cell-trafficking studies.
Animals↗
Transcranial laser doppler mapping of activation flow coupling of the rat somatosensory cortex.
Signal averaged laser Doppler (LD) through a thinned skull over the rat somatosensory cortex was used to map the spatial and temporal characteristics of activation-flow coupling, the change in regional cerebral blood flow (CBF) due to neuronal activation, in response to electrical forepaw stimulation. The location of maximal changes in amplitude of the LD response was reproducibly recorded at 4-5 mm lateral to Bregma. This location is very similar but slightly posterior and lateral to results obtained from electrophysiological, magnetic resonance imaging (MRI), and optical imaging studies. The latency of the activation-flow coupling (AFC) response was inversely correlated to response amplitude, with shorter latencies at positions of maximal amplitude.
Animals↗
Magneto/optical annexin V, a multimodal protein.
Multimodal proteins, or proteins labeled with both fluorescent and magnetic reporter groups, can be used in a wide range of applications including FACS or fluorescence microscopy, MRI and or near-infrared based optical imaging, or to fractionate cells by magnetic cell sorting. A problem with multimodal proteins, however, is the need to maximize bioactivity, often achieved by minimizing the number of modification points of the protein, while attaching fluorescent and magnetic labels. Here we describe the synthesis of a magneto/optical form of annexin V, achieved by reacting the amino-CLIO nanoparticle with Cy5.5 and SPDP, to produce a fluorescent, sulfhydryl reactive nanoparticle. A single reactive sulfhydryl group was added to annexin V by reaction with SATA that preserved the protein's ability to bind apoptotic Jurkat T cells. Reacting SATAylated annexin V with an SPDP activated nanoparticle yielded Anx-CLIO-Cy5.5, a magneto/optical form of annexin V. The binding of Anx-CLIO-Cy5.5 was specific for apoptotic Jurkat T cells and had an EC(50) of 3.66 nM. This was comparable to the strength of the interaction of unmodified annexin V with apoptotic cells, measured as the displacement of FITC-annexin by annexin V (2.4 nM). Our conjugation strategy preserves the strength of the interaction between annexin V and apoptotic cells, while yielding a probe, Anx-CLIO-Cy5.5, that is readily detectable by standard MR imaging or NIRF optical methods.
Annexin A5↗
Molecular imaging of hepatocellular carcinoma.
Molecular imaging may be defined as spatially localized and/or temporally resolved sensing of molecular and cellular processes in vivo. An imageable molecular event may be the result of the overexpression of a gene that produces a specific messenger RNA. The overexpressed protein could be an enzyme or could be incorporated into cell-surface transporters or receptors. Any step of this process is a potential target for molecular imaging. Current molecular imaging modalities include magnetic resonance imaging, nuclear imaging, ultrasound, and optical imaging. Nuclear medicine has been at the forefront of molecular imaging because of the relatively high sensitivity to detect nanomolar or picomolar quantities of the radiolabeled imaging probe. Imaging has had a central role in the diagnosis of hepatocellular carcinoma (HCC), which is considered the fifth most frequent malignancy worldwide. Nuclear imaging was one of the earlier modalities used for liver imaging. Traditional tracers included technetium 99m ( 99m Tc) sulfur colloid, gallium 67, and 99m Tc iminodiacetate acid analogues. Other less traditional probes include 99m Tc diethylenetriamine pentaacetic acid-galactosyl-human serum albumin for evaluation of functional liver volume and 99m Tc-labeled tetrofosmin and methoxisobutylisonitrile for detecting drug resistance. Fluorodeoxyglucose is the most widely used probe for positron emission tomography (PET) tumor imaging; however, carbon 11-labeled acetate appears to show improved sensitivity and specificity for HCC. Oxygen 15 PET imaging allows for the measurement of hepatic and tumor blood flow. Difficulties developing specific imaging methods for HCC are caused by the lack of obvious specific molecular targets, problems with drug delivery, and poor contrast-to-noise. No magic molecular imaging method exists today to accurately detect, characterize, and monitor HCC in vivo.
Carcinoma, Hepatocellular↗
Imaging angiogenesis: applications and potential for drug development.
Recognition of the importance of angiogenesis to tumor growth and metastasis has led to efforts to develop new drugs that are targeted to angiogenic vasculature. Clinical trials of these agents are challenging, both because there is no agreed upon method of establishing the correct dosage for drugs whose mechanism of action is not primarily cytotoxic and because of the long time it takes to determine whether such drugs have a clinical effect. Therefore, there is a need for rapid and effective biomarkers to establish drug dosage and monitor clinical response. This review addresses the potential of imaging as a way to accurately and reliably assess changes in angiogenic vasculature in response to therapy. We describe the advantages and disadvantages of several imaging modalities, including positron emission tomography, x-ray computed tomography, magnetic resonance imaging, ultrasound, and optical imaging, for imaging angiogenic vasculature. We also discuss the analytic methods used to derive blood flow, blood volume, empirical semiquantitative hemodynamic parameters, and quantitative hemodynamic parameters from pharmacokinetic modeling. We examine the validity of these methods, citing studies that test correlations between data derived from imaging and data derived from other established methods, their reproducibility, and correlations between imaging-derived hemodynamic parameters and other pathologic indicators, such as microvessel density, pathology score, and disease outcome. Finally, we discuss which imaging methods are most likely to have the sensitivity and reliability required for monitoring responses to cancer therapy and describe ways in which imaging has been used in clinical trials to date.
Angiogenesis Inhibitors↗
Tumor cell invasion of model 3-dimensional matrices: demonstration of migratory pathways, collagen disruption, and intercellular cooperation.
We report a novel 3-dimensional model for visualizing tumor cell migration across a nylon mesh-supported gelatin matrix. To visualize migration across these model barriers, cell proteolytic activity of the pericellular matrix was detected using Bodipy-BSA (fluorescent upon proteolysis) and DQ collagen (fluorescent upon collagenase activity). For 3-dimensional image reconstruction, multiple optical images at sequential z axis positions were deconvoluted by computer analysis. Specificity was indicated using well-known inhibitors. Using these fluorescent proteolysis markers and imaging methods, we have directly demonstrated proteolytic and collagenolytic activity during tumor cell invasion. Moreover, it is possible to visualize migratory pathways followed by tumor cells during matrix invasion. Using cells of differing invasive potentials (uPAR-negative T-47D wild-type and uPAR-positive T-47D A2--1 cells), we show that the presence of the T-47D-A2--1 cells facilitates the entry of T-47D wild-type cells into the matrix. In some cases, wild-type cells follow T-47D A2--1 cells into the matrix whereas other T-47D-wild-type cells appear to enter without the direct intervention of T-47D A2--1 cells. Thus, we have developed a new 3-dimensional model of tumor cell invasion, demonstrated protein and collagen disruption, mapped the pathways followed by tumor cells during migration through an extracellular matrix, and illustrated cross-talk among tumor cell populations during invasion.
Cell Movement↗
Imaging molecular and cellular events in transplantation.
Imaging methods such as nuclear medicine (including positron emission tomography), magnetic resonance imaging, ultrasound, and optical imaging can be used to provide information about the expression of genes, and the location of molecules and cells in intact animals or patients. In the setting of transplantation, this will allow monitoring of inflammatory responses, as well as the state of the graft. In this review, the advantages and disadvantages of different approaches to imaging will be discussed, as well as their potential application to transplantation.
Biomarkers↗
Image registration and distortion correction in ion microscopy.
We present a method whereby the geometric registration of a series of ion microscopic images is performed by applying a two-step procedure. After applying a global linear transformation that corrects for geometric differences, a non-linear elastic transform is used in order to match local properties and structures of the images. Transformation parameters are computed on the basis of shape-specific points in the images. Distortion correction is achieved by relating ion images to the optical image of the same field and by using the two-step algorithm to register the images. This methodology is evaluated on synthetic misaligned objects and on thyroid tissue images.
Animals↗
Functional mapping of horizontal connections in developing ferret visual cortex: experiments and modeling.
In cat striate cortex, patchy horizontal axonal projections link columns of similar orientation specificity. To assess the physiological correlates of such clustered projections, a new multisite stimulation technique was used to functionally map the pattern of horizontal synaptic inputs onto single layer 2/3 cells within tangential slices of developing ferret visual cortex. Twenty-four separate sets of horizontal fibers were stimulated within a 1200 microns strip of cortex, while evoked synaptic responses were recorded using whole-cell patch methods. For most cells, input maps demonstrated the presence of clustered horizontal connections in which multiple strong and weak synaptic responses were alternately evoked across the stimulated cortical region. Recordings from up to nine cells in a single slice revealed that patterns of synaptic input were closely correlated for cells in close proximity, and that this correlation decreased with distance, with no correlation at distances greater than 500 microns. To determine whether these physiological results were consistent with the known anatomical linkage of iso-orientation columns by clustered horizontal connections, mathematical analysis and computer simulations were performed upon orientation tuning maps obtained from optical imaging of activity-dependent intrinsic signals in mature ferret visual cortex. Optical imaging revealed an organization of iso-orientation domains consisting of broad regions of cortex across which orientation preference smoothly varied, together with "orientation centers" around which orientation preference was arranged in a pinwheel manner. The distribution of synaptic connections between different cortical sites was simulated by a model of functionally linked iso- orientation columns. Simulated synaptic input maps, generated by the same stimulation and recording arrangements used in our experimental protocol, accurately reproduced the observed patterns of clustered inputs onto experimentally recorded cells. These results indicate that even at the time of eye opening, prior to extensive visual experience, most cells receive patterns of synaptic inputs consistent with a clustered organization of horizontal connections that functionally link iso-orientation columns.
Animals↗
Advances in optical spectroscopy and imaging of breast lesions.
A review is presented of recent advances in optical imaging and spectroscopy and the use of light for addressing breast cancer issues. Spectroscopic techniques offer the means to characterize tissue components and obtain functional information in real time. Three-dimensional optical imaging of the breast using various illumination and signal collection schemes in combination with image reconstruction algorithms may provide a new tool for cancer detection and treatment monitoring.
Breast Cyst↗
MR imaging of optic nerve lesions: value of gadopentetate dimeglumine and fat-suppression technique.
Eleven patients with known or suspected optic nerve lesions and eight normal subjects were examined with spin-echo technique at 1.5 T with unenhanced T1-weighted imaging, IV gadopentetate-dimeglumine-enhanced T1-weighted imaging, and enhanced T1-weighted imaging with fat suppression. Two pathologically proved and four presumed optic nerve meningiomas demonstrated significant enhancement and were best seen with the fat-suppression technique. None of the three presumed optic nerve gliomas nor the optic nerves of normal subjects demonstrated qualitative enhancement. We conclude that the use of a fat-suppression technique with gadopentetate dimeglumine enhancement improves delineation of enhancing optic nerve lesions. This technique should be useful for evaluating other anatomic regions where enhancing tissue marginates fat.
Adult↗
Comparison of optic nerve imaging methods to distinguish normal eyes from those with glaucoma.
PURPOSE: To compare the ability of qualitative assessment of optic nerve head stereophotographs (ONHPs), confocal scanning laser ophthalmoscopy (CSLO), scanning laser polarimetry (SLP), and optical coherence tomography (OCT) to distinguish normal eyes from those with early to moderate glaucomatous visual field defects. METHODS: Eighty-nine eyes (63 normal, 63 age-matched with glaucoma) of 89 subjects more than 40 years of age were studied. Receiver operating characteristic (ROC) curves were generated from discriminant analysis of CSLO, SLP, and OCT measurements and from ONHP scores. Sensitivity at 80% and specificity at 90% were calculated. Differences between individual methods and combinations of methods were assessed for statistical significance. Agreement on categorization between methods (kappa) was assessed. RESULTS: The average visual field mean deviation (MD +/- SD) in patients with glaucoma was -3.9 +/- 2.2 dB, and the average pattern standard deviation (PSD) was 4.7 +/- 3.4 dB. In normal subjects the average MD was 0.1 +/- 0.9 dB and the average PSD was 1.5 +/- 0.3 dB. Optimal sensitivities, specificities, and areas under ROC curves were, respectively: ONHP (0.94, 0.87, 0.93), CSLO (0.84, 0.90, 0.92), SLP (0.89, 0.87, 0.94), and OCT (0.82, 0.84, 0.88). Best agreement on categorization (kappa) was between ONHPs and CSLO (0.70). The ROC area for the combination of methods was 0.99, higher than for any method alone. The ROC area for the combination of methods was significantly better than the CLSO rim area (P = 0.012) and the OCT retinal nerve fiber layer (RNFL) thickness (P = 0.002). CONCLUSIONS: The quantitative methods CSLO, SLP, and OCT were no better than qualitative assessment of disc ONHPs by experienced observers at distinguishing normal eyes from those with early to moderate glaucoma. A combination of the imaging methods significantly improves this capability.
Diagnostic Techniques, Ophthalmological↗
Voltage-sensitive dye imaging of intervibrissal fur-evoked activity in the rat somatosensory cortex.
The intervibrissal fur-evoked activity in the rat somatosensory cortex was investigated using high-resolution optical imaging with a voltage-sensitive dye. The optical imaging revealed that the intervibrissal fur representation forms a U-shaped band around the borders of the posteromedial barrel subfield (PMBSF), and that this representation is characterized by a rostral-to-caudal somatotopic organization. When GABA(A)-mediated inhibition was partially suppressed by treatment with bicuculline, stimulation of the intervibrissal fur elicited spreading of an excitation wave in an area outside the PMBSF. The spreading wave propagated in both directions along the aforementioned U-shaped band of cortex, but barely invaded the center of the PMBSF. These imaging results suggest a distinct subdivision of cortex adjacent to, but outside, the PMBSF in the rat somatosensory cortex; this region receives input from intervibrissal fur, and seems to process its sensory information through well-developed local horizontal connections.
Animals↗
[Low visual acuity, disorders of the visual field: how to adapt the imaging of optical pathways to clinical practice?].
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Diagnostic Imaging↗
Magnetic resonance imaging in optic neuritis due to giant cell arteritis.
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Administration, Oral↗
Magnetic resonance imaging of optic nerve meningiomas. Enhancement with gadolinium-DTPA.
Six patients with optic nerve sheath meningiomas were studied with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) to evaluate intracranial extension. The intraorbital and intracranial tumors were isointense to cortical gray matter on T1-weighted studies without contrast in all patients. After Gd-DTPA, three patients showed mild enhancement of the intraorbital tumor, whereas five of six patients showed vivid enhancement of the intracranial tumor. In four cases, the intracranial extension could not be definitely seen on MRI without Gd-DTPA. Two patients had proton density and T2-weighted studies; in each case, the intraorbital tumor remained nearly isointense. The intracranial tumor was suggested in one patient on T2-weighted studies, but was poorly defined. Gadolinium-DTPA has proved valuable in detecting intracranial extension of optic nerve meningiomas that are not well visualized on standard MRI without contrast.
Adult↗