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All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast.

ABSTRACT: Optical molecular imaging in small animals harnesses the power of highly specific and biocompatible contrast agents for drug development and disease research1-7. However, the widespread adoption of in vivo optical imaging has been inhibited by its inability to clearly resolve and identify targeted internal organs. Optical tomography8-11 and combined X-ray and micro-computed tomography (micro-CT)12 approaches developed to address this problem are generally expensive, complex or incapable of true anatomical co-registration. Here, we present a remarkably simple all-optical method that can generate co-registered anatomical maps of a mouse's internal organs, while also acquiring in vivo molecular imaging data. The technique uses a time series of images acquired after injection of an inert dye. Differences in the dye's in vivo biodistribution dynamics allow precise delineation and identification of major organs. Such co-registered anatomical maps permit longitudinal organ identification irrespective of repositioning or weight gain, thereby promising greatly improved accuracy and versatility for studies of orthotopic disease, diagnostics and therapies.

SUBMITTER: Hillman EM

PROVIDER: S-EPMC2575379 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast.

Hillman Elizabeth M C EM Moore Anna A

Nature photonics 20070101 9

Optical molecular imaging in small animals harnesses the power of highly specific and biocompatible contrast agents for drug development and disease research1-7. However, the widespread adoption of in vivo optical imaging has been inhibited by its inability to clearly resolve and identify targeted internal organs. Optical tomography8-11 and combined X-ray and micro-computed tomography (micro-CT)12 approaches developed to address this problem are generally expensive, complex or incapable of true ...[more]

PMID: 18974848

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Project description:Iterative reconstruction algorithms are becoming more commonly employed in positron emission tomography (PET) imaging; however, the quantitative accuracy of the reconstructed images still requires validation for various levels of contrast and counting statistics.The authors present an evaluation of the quantitative accuracy of the 3D maximum a posteriori (3D-MAP) image reconstruction algorithm for dynamic PET imaging with comparisons to two of the most widely used reconstruction algorithms: the 2D filtered-backprojection (2D-FBP) and 2D-ordered subsets expectation maximization (2D-OSEM) on the Siemens microPET scanners. The study was performed for various levels of count density encountered in typical dynamic scanning as well as the imaging of cardiac activity concentration in small animal studies on the Focus 120. Specially designed phantoms were used for evaluation of the spatial resolution, image quality, and quantitative accuracy. A normal mouse was employed to evaluate the accuracy of the blood time activity concentration extracted from left ventricle regions of interest (ROIs) within the images as compared to the actual blood activity concentration measured from arterial blood sampling.For MAP reconstructions, the spatial resolution and contrast have been found to reach a stable value after 20 iterations independent of the β values (i.e., hyper parameter which controls the weight of the penalty term) and count density within the frame. The spatial resolution obtained with 3D-MAP reaches values of ∼1.0 mm with a β of 0.01 while the 2D-FBP has value of 1.8 mm and 2D-OSEM has a value of 1.6 mm. It has been observed that the lower the hyper parameter β used in MAP, more iterations are needed to reach the stable noise level (i.e., image roughness). The spatial resolution is improved by using a lower β value at the expense of higher image noise. However, with similar noise level the spatial resolution achieved by 3D-MAP was observed to be better than that by 2D-FBP or 2D-OSEM. Using an image quality phantom containing hot spheres, the estimated activity concentration in the largest sphere has the expected concentration relative to the background area for all the MAP images. The obtained recovery coefficients have been also shown to be almost independent of the count density. 2D-FBP and 2D-OSEM do not perform as well, yielding recovery coefficients lower than those observed with 3D-MAP (approximately 33% lower for the smallest sphere). However, a small positive bias was observed in MAP reconstructed images for frames of very low count density. This bias is present in the uniform area for count density of less than 0.05 × 10(6) counts/ml. For the dynamic mouse study, it was observed that 3D-MAP (even gated at diastole) cannot predict accurately the blood activity concentration due to residual spill-over activity from the myocardium into the left ventricle (approximately 15%). However, 3D-MAP predicts blood activity concentration closer to blood sampling than 2D-FBP.The authors observed that 3D-MAP produces more accurate activity concentration estimates than 2D-FBP or 2D-OSEM at all practical levels of statistics and contrasts due to improved spatial resolution leading to lesser partial volume effect.

Dataset Information

All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast.

Publications

All-optical anatomical co-registration for molecular imaging of small animals using dynamic contrast.

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