Quantitative optical coherence tomographic elastography: method for assessing arterial mechanical properties.

Optical coherence tomography elastography represents a potentially attractive new technique for measuring elastic properties of tissues on a micron scale. In this study, the feasibility of optical coherence tomography (OCT) to study the mechanical properties of phantoms and atherosclerotic arterial samples is reported. The elastic modulus of tissue-mimicking phantoms was measured using OCT and correlated with mechanical measurements. The results indicate that elastography based on OCT represents an attractive technique for evaluating the mechanical properties of tissues.

Optical coherence tomographic elastography technique for measuring deformation and strain of atherosclerotic tissues.

OBJECTIVES: To evaluate optical coherence tomographic elastography as a method for assessing the elastic properties of atherosclerotic plaque and the parameters that influence interpretation. METHODS: Phantoms and aorta were examined in vitro to quantify speckle modulation and measure the displacement and strain maps. A correlation method was used as a speckle tracking technique for measuring axial and lateral displacement vectors and calculation of strain maps. The influence of correlation kernel size on accuracy of the method was evaluated. RESULTS: In terms of a percentage error between calculated and measured displacements, the best results for phantoms were obtained with a 41 x 41 kernel (1.88% error). For both phantom and aorta images, it was found that, with the increasing size of cross correlation kernel, the axial and lateral displacement maps are less noisy and the displacement vectors are more clearly defined. However, the large kernels tend to average out the differences in displacements of small particles in phantoms and decrease the ability of speckle tracking to make microstructural assessments. Therefore, it is important to select kernel size carefully, based on the image features. CONCLUSIONS: Optical tomographic elastography can be used to assess the microstructural properties of atherosclerotic tissue at micrometre scale resolution, but preselected analysis criteria must be understood in a critical interpretation of the results.

Evaluation of the adaptive speckle suppression filter for coronary optical coherence tomography imaging.

During the last few years, optical coherence tomography (OCT) has demonstrated considerable promise as a method of high-resolution intravascular imaging. The goal of this study was to apply and to test the applicability of the rotating kernel transformation (RKT) technique to the speckle reduction and enhancement of OCT images. The technique is locally adaptive. It is based on sequential application of directional masks and selection of the maximum of all outputs. This method enhances the image features by emphasizing thin edges while suppressing a noisy background. Qualitatively, the RKT algorithm provides noticeable improvement over the original image. All processed images are smoother and have better-defined borders of media, intima, and plaque. The quantitative evaluation of RKT performance showed that in terms of average contrast-to-noise ratio, there is a significant improvement in image quality between original and enhanced images. The RKT image enhancement technique shows great promise in improving OCT images for superior boundary identification.

YM872, a highly water-soluble AMPA receptor antagonist, preserves the hemodynamic penumbra and reduces brain injury after permanent focal ischemia in rats.

BACKGROUND AND PURPOSE: We recently described an image analysis technique based on the temporal correlation mapping (TCM) of injected contrast agents that can be used to distinguish the hemodynamic core and hemodynamic penumbra after focal ischemia. In this study we used this technique for the first time to investigate the effects of the water-soluble AMPA receptor antagonist YM872 in permanent focal ischemia. METHODS: Fischer 344 rats were subjected to permanent occlusion of the middle cerebral artery. Approximately 30 minutes after ischemia, functional CT images were collected with the use of a dynamic scanning protocol with bolus injections of nonionic contrast agent iohexol (1 mL/kg). TCM analysis defined the distributions of hemodynamic core and hemodynamic penumbra. Cerebral perfusion indices were calculated on the basis of the area under the first-pass transit curves. One hour after ischemia, animals were randomly treated with YM872 (n=8, 20 mg/kg per hour over 4 hours) or normal saline (n=10). Twenty-four hours later, neurological deficits were evaluated, and conventional CT and triphenyltetrazolium chloride staining were used to define volumes of ischemic damage. RESULTS: At 24 hours after ischemia, hypodense lesions were visible on conventional CT scans that were highly correlated with triphenyltetrazolium chloride lesion volumes. YM872 improved neurological deficits and reduced volumes of ischemic damage in cortex (90+/-14 versus 170+/-16 mm3 in controls) but not striatum (57+/-14 versus 79+/-6 mm3 in controls). Comparison of early TCM images with conventional CT scans of ischemic injury showed that the hemodynamic core was always damaged in all rats. In controls, 54% of the tissue within the hemodynamic penumbra evolved into ischemic damage compared with 24% in YM872-treated rats. Furthermore, the perfusion index corresponding to the ischemic damage threshold was significantly reduced by YM872 (28+/-2% versus 37+/-2% in controls). CONCLUSIONS: These results indicate that YM872 is a neuroprotective compound that ameliorates the deterioration of the hemodynamic penumbra after focal ischemia.

Temporal correlation mapping analysis of the hemodynamic penumbra in mutant mice deficient in endothelial nitric oxide synthase gene expression.

BACKGROUND AND PURPOSE: Mice containing deletions in the genes encoding nitric oxide (NO) synthase have been useful to dissect the role of NO in cerebral ischemia. We recently reported that mice lacking expression of the endothelial isoform of NO synthase (eNOS) develop larger infarcts after middle cerebral artery occlusion. Because NO or a related product of NO synthase activity is important for relaxation of cerebral blood vessels, we examined for possible hemodynamic differences in the peri-ischemic zone of eNOS-deficient and wild-type mice after middle cerebral artery occlusion using functional CT scanning techniques. METHODS: Wild-type SV129 mice (n = 10) and mice deficient in eNOS gene expression (n = 10) were subjected to middle cerebral artery occlusion under halothane anesthesia. Thirty minutes after ischemia, functional CT scanning was performed with dynamic scanning protocols to measure the cerebral transit profiles of injected contrast agents. A temporal correlation mapping technique was used to analyze the pattern of hemodynamic perturbations based on alterations in the shape of the cerebral transit profiles. Statistical thresholds defined the hemodynamic core and penumbra. RESULTS: Hemodynamic deficits were more severe in the mutant than wild-type mouse. When expressed as a percentage of the total insult, core areas were significantly increased in mutant mice (39.8 +/- 3.7%) compared with wild types (28.8 +/- 3.4%). Conversely, areas of the hemodynamic penumbra were significantly smaller in mice deficient in eNOS activity (60.2 +/- 3.7%) than in wild-type mice (71.2 +/- 3.4%). Furthermore, the calculated relative perfusion index within the hemodynamic penumbra was significantly lower in the group with eNOS gene deletion (35.6 +/- 1.5% in mutants versus 43.0 +/- 2.4% in wild types). CONCLUSIONS: These data indicate that mice lacking eNOS expression show a greater degree of hemodynamic compromise after middle cerebral artery occlusion and suggest that a product of eNOS activity (eg. NO) may protect brain after focal cerebral ischemia, possibly by improving blood flow within the penumbral zone.

Hemodynamic alterations in focal cerebral ischemia: temporal correlation analysis for functional imaging.

We describe a novel approach for analysing the hemodynamic alterations that result after focal cerebral ischemia. This approach utilizes a temporal correlation analysis of first pass transit data obtained with functional imaging. First pass transits of injected contrast agents are measured with dynamic CT scanning. Normal transit profiles are obtained from contralateral cortical regions to serve as reference profiles. Normalized correlations are then calculated to compare transit profiles from each individual pixel within the brain to the normal reference profile. The normalized correlation coefficient is used as a measure of temporal similarity to quantitatively assess deviations from normal hemodynamics. The method is based on the premise that perturbed hemodynamics are manifested as changes in the shape of the cerebral transit profiles. Correlation maps are produced that display regional alterations in cerebral hemodynamics. Results from rabbit (n=4) and rat (n=4) models of focal ischemia are presented. In the normal contralateral hemisphere, correlation values range from 0.83-0.93 with coefficients of variation of less than 3-4% . The ischemic core is comprised of regions without significant bolus transit. The peripheral zones that lie between normal brain and the ischemic core are composed of intermediate correlation values. By setting statistical thresholds (mean minus 2SD, p < 0.05), we quantitatively define these intermediate zones as the hemodynamic penumbra, i.e. regions where the shape of the first pass transit profile has been altered. The resulting correlation maps clearly image gradients of altered cerebral hemodynamics. Perfusion indices calculated based on transit profile peaks revealed that the penumbral zones possess reduced perfusion on the order of about 40 percent of contralateral values. In summary, we believe that temporal correlation analysis of first pass transit profiles can be used to image the hemodynamic penumbra in focal cerebral ischemia.

Evaluation of selected two-dimensional segmentation techniques for computed tomography quantitation of lymph nodes.

RATIONALE AND OBJECTIVES: As contrast agents that selectively target normal lymph nodes are undergoing development and evaluation, it has become important to accurately and reproducibly determine nodal boundaries to study the agents and determine such values as lymph node area or mean nodal contrast concentration. This study was performed to evaluate the accuracy of different two-dimensional computer segmentation methods, tested on acrylic phantoms constructed to imitate the appearance of lymph nodes surrounded by fat. METHODS: Five segmentation techniques (manual tracing, semiautomatic local criteria threshold selection, Sobel/watershed technique, interactive deformable contour algorithm and thresholding) were evaluated using phantoms. Subsequently, the first three methods were applied to the images of enhanced lymph nodes in rabbits. RESULTS: Minimum errors in phantom area measurement (< 5%) and interoperator variation (< 5%) were seen with the Sobel/watershed technique and the interactive deformable contour algorithm. These two techniques were significantly better than thresholding and semiautomated thresholding based on local properties. CONCLUSION: Methods based on Sobel edge detection offer more objective tools than thresholding methods for segmenting objects similar to lymph nodes in computed tomography images. Both methods, Sobel/watershed and interactive deformable contour algorithm, are fast and have simple user interfaces.

Temporal correlation analysis of penumbral dynamics in focal cerebral ischemia.

A novel temporal correlation technique was used to map the first-pass transit of iodinated contrast agents through the brain. Transit profiles after bolus injections were measured with dynamic computed tomography (CT) scanning (1 image/s over 50 s). A rabbit model of focal cerebral ischemia (n = 6) was used, and dynamic CT scans were performed at 30, 60, 90, and 120 min postocclusion. Within the ischemic core, no bolus transit was detectable, demonstrating that complete ischemia was present after arterial occlusion. In the periphery of the ischemic distribution, transit dynamics showed smaller peaks, broadened profiles, and overall delay in bolus transit. A cross-correlation method was used to generate maps of delays in ischemic transit profiles compared with normal transit profiles from the contralateral hemisphere. These maps showed that penumbral regions surrounding the ischemic core had significantly delayed bolus transit profiles. Enlargement of the ischemic core over time (from 30 to 120 min postocclusion) was primarily accomplished by the progressive deterioration of the penumbral regions. These results suggest that (a) temporal correlation methods can define regions of abnormal perfusion in focal cerebral ischemia, (b) peripheral regions of focal cerebral ischemia are characterized by delays in bolus transit profiles, and (c) these regions of bolus transit delay deteriorate over time and thus represent a hemodynamic penumbra.

Applications of similarity mapping in dynamic MRI.

Dynamic images are temporal sequences of images, where the intensities of certain regions of interest (ROI's) change with time, whereas anatomical structures remain stationary. Here, new applications of dynamic image analysis, called similarity mapping, are reviewed. Similarity mapping identifies regions in a dynamic image sequence according to their temporal similarity or dissimilarity with respect to a reference ROI. Pixels in the resulting similarity map whose temporal sequence is similar to the reference ROI have high correlation values and are bright, while those with low correlation values are dark. Therefore, similarity mapping segments structures in a dynamic image sequence based on their temporal responses rather than spatial properties. The authors describe the abilities of similarity mapping to identify different image structures present in several dynamic MRI datasets with potential clinical value. They demonstrate that similarity mapping technique has been successful in identifying the following structures: 1) renal cortex and medulla, 2) activated areas of the brain during photic stimulation, 3) ischemia in the left coronary artery territory, 4) lung tumor, 5) tentorial meningioma, and 6) a region of focal ischemia in brain.

A comparative analysis of similarity mapping and eigenimaging as applied to dynamic MR imaging of a low grade astrocytoma.

This paper compares the abilities of similarity mapping and eigenimaging for the purpose of identifying (segmenting) different image structures in dynamic MR imaging. As an illustrative example a case of dynamic images with a low grade astrocytoma was chosen. It was found that the similarity mapping was more successful than eigenimaging in determining the extent and position of a low grade astrocytoma. Also, similarity mapping was able to identify another region with a different and uncorrelated temporal pattern that was later diagnosed as a cyst.

Measurement of renal transit of gadopentetate dimeglumine with echo-planar MR imaging.

Times of peak gadolinium concentration ([Gd]) after intravenous (IV) and left ventricular (LV) bolus injection of gadopentetate dimeglumine were determined in renal cortex and medulla in normal rabbits and in rabbits after saline load (overhydration) or hemorrhage (dehydration). Magnetic resonance images were obtained with echo-planar inversion-recovery sequences, and signal intensity-versus-time curves in cortical and medullary regions of interest were converted to [Gd]-versus-time curves. Cortical perfusion measured with microspheres demonstrated that the three physiologic states were significantly different. There were three separate [Gd] peaks in both the cortex and medulla as the bolus moved from one anatomic compartment to the next. The first cortical peak occurred sooner after LV than after IV bolus injection (P < .05) and later in dehydrated than in normal and overhydrated rabbits (P < .05). The first medullary peak always followed the first cortical peak by about 6-10 seconds and mirrored the cortical patterns. The second and third cortical peaks were consistent with proximal and distal tubular transit. These peaks similarly showed faster response to LV than IV injection and were delayed by hemorrhage. The authors conclude that quantitative physiologic information can be obtained with dynamic contrast-enhanced MR imaging of the kidney.

Percutaneous CT lymphography with perflubron: imaging efficacy in rabbits and monkeys.

PURPOSE: To evaluate the imaging efficacy of percutaneous lymphography performed with injection of perflubron emulsions and computed tomography (CT). MATERIALS AND METHODS: Thin-section CT was used to image lymph nodes in 116 rabbits and six monkeys. Quantitative measures of regional lymph node enhancement were obtained 4 hours to 21 days after subcutaneous injection of perflubron (0.1-0.5 mL per injection site). Lymph node enhancement was calculated in Hounsfield units and converted to bromine concentration with standards that were imaged at the same time. RESULTS: Excellent enhancement of regional lymph nodes in both groups of animals was obtained. Nodal enhancement was linearly related to dose and was sustained for 20 days; maximum enhancement was seen 2 days after injection. Massage of the injection site increased delivery of the perflubron emulsion to regional lymph nodes. CONCLUSION: In rabbits and monkeys, percutaneous CT lymphography effectively depicts the intranodal distribution of macrophages in normal lymph nodes.

Temporal correlation images derived from sequential MR scans.

In this paper a new technique is presented for measuring the local temporal changes and correlation between them on spatially aligned image sequences. A temporal correlation image is derived from a sequence of static images (frames). The method is illustrated in an application to the dynamic MRI of the rabbit kidney following bolus injection of Gd-DTPA. The similarity maps clearly separate the dynamic response of the cortex to the indicator from that of the medulla and, therefore, segment the kidney into two regions. Regions with different temporal dynamics can be displayed in different colors using a lookup table designed for that purpose.

Evaluation of algorithms for ratio imaging in fluorescence microscopy.

Ratio imaging in fluorescence microscopy is used in measuring parameters such as pH, pCa, cytoplasmic porosity, and the relative concentration of fluorescent analogs within single cells. The fastest method for ratio imaging is to use lookup tables on special-purpose image processors. Since lookup tables store integers in integer addresses, using a lookup table will generate rounding errors. The magnitude of the error will depend on the transformation performed and on the number of levels used in the lookup table. We examined ratio imaging by lookup table and computed the errors generated by both inversion and log subtraction methods. Both uniformly fluorescing fields and fluorescing cell images were employed to provide data for use in confirming our calculations and illustrating both the magnitude and spatial incidence of errors. It is shown that, through proper design of lookup tables, a significant reduction can be made in the errors generated in comparison with common methods available in most image processors.

Fluorescence ratio imaging microscopy: temporal and spatial measurements of cytoplasmic pH.

Fluorescence ratio imaging microscopy (Tanasugarn, L., P. McNeil, G. Reynolds, and D. L. Taylor, 1984, J. Cell Biol., 98:717-724) has been used to measure the spatial variations in cytoplasmic pH of individual quiescent and nonquiescent Swiss 3T3 cells. Fundamental issues of ratio imaging that permit precise and accurate temporal and spatial measurements have been addressed including: excitation light levels, lamp operation, intracellular probe concentrations, methods of threshold selection, photobleaching, and spatial signal-to-noise ratio measurements. Subcellular measurements can be measured accurately (less than 3% coefficient of variation) in an area of 3.65 microns 2 with the present imaging system. Quiescent Swiss 3T3 cells have a measured cytoplasmic pH of 7.09 (0.01 SEM), whereas nonquiescent cells have a pH of 7.35 (0.01 SEM) in the presence of bicarbonate buffer. A unimodal distribution of mean cytoplasmic pH in both quiescent and nonquiescent cells was identified from populations of cells measured on a cell by cell basis. Therefore, unlike earlier studies based on cell population averages, it can be stated that cells in each population exhibit a narrow range of cytoplasmic pH. However, the mean cytoplasmic pH can change based on the physiological state of the cells. In addition, there appears to be little, if any, spatial variation in cytoplasmic pH in either quiescent or nonquiescent Swiss 3T3 cells. The pH within the nucleus was always the same as the surrounding cytoplasm. These values will serve as a reference point for investigating the role of temporal and spatial variations in cytoplasmic pH in a variety of cellular processes including growth control and cell movement.