Deep and Clear Optical Imaging of Thick Inhomogeneous Samples

Inhomogeneity in thick biological specimens results in poor imaging by light microscopy, which deteriorates as the focal plane moves deeper into the specimen. Here, we have combined selective plane illumination microscopy (SPIM) with wavefront sensor adaptive optics (wao). Our waoSPIM is based on a direct wavefront measure using a Hartmann-Shack wavefront sensor and fluorescent beads as point source emitters. We demonstrate the use of this waoSPIM method to correct distortions in three-dimensional biological imaging and to improve the quality of images from deep within thick inhomogeneous samples

Validation of 3\u27-deoxy-3\u27-[18F]-fluorothymidine positron emission tomography for image-guidance in biologically adaptive radiotherapy

Accelerated tumor cell repopulation during radiation therapy is one of the leading causes for low survival rates of head-and-neck cancer patients. The therapeutic effectiveness of radiotherapy could be improved by selectively targeting proliferating tumor subvolumes with higher doses of radiation. Positron emission tomography (PET) imaging with 3´-deoxy-3´-[18F]-fluorothymidine (FLT) has shown great potential as a non-invasive approach to characterizing the proliferation status of tumors. This thesis focuses on histopathological validation of FLT PET imaging specifically for image-guidance applications in biologically adaptive radiotherapy. The lack of experimental data supporting the use of FLT PET imaging for radiotherapy guidance is addressed by developing a novel methodology for histopathological validation of PET imaging. Using this new approach, the spatial concordance between the intratumoral pattern of FLT uptake and the spatial distribution of cell proliferation is demonstrated in animal tumors. First, a two-dimensional analysis is conducted comparing the microscopic FLT uptake as imaged with autoradiography and the distribution of active cell proliferation markers imaged with immunofluorescent microscopy. It was observed that when tumors present a pattern of cell proliferation that is highly dispersed throughout the tumor, even high-resolution imaging modalities such as autoradiography could not accurately determine the extent and spatial distribution of proliferative tumor subvolumes. While microscopic spatial coincidence between high FLT uptake regions and actively proliferative subvolumes was demonstrated in tumors with highly compartmentalized/aggregated features of cell proliferation, there were no conclusive results across the entire set of utilized tumor specimens. This emphasized the need for addressing the limited resolution of FLT PET when imaging microscopic patterns of cell proliferation. This issue was emphasized in the second part of the thesis where the spatial concordance between volumes segmented on FLT simulated FLT PET images and the three dimensional spatial distribution of cell proliferation markers was analyzed

Comparison of CBCT based synthetic CT methods suitable for proton dose calculations in adaptive proton therapy

In-room imaging is a prerequisite for adaptive proton therapy. The use of onboard cone-beam computed tomography (CBCT) imaging, which is routinely acquired for patient position verification, can enable daily dose reconstructions and plan adaptation decisions. Image quality deficiencies though, hamper dose calculation accuracy and make corrections of CBCTs a necessity. This study compared three methods to correct CBCTs and create synthetic CTs that are suitable for proton dose calculations. CBCTs, planning CTs and repeated CTs (rCT) from 33 H&N cancer patients were used to compare a deep convolutional neural network (DCNN), deformable image registration (DIR) and an analytical image-based correction method (AIC) for synthetic CT (sCT) generation. Image quality of sCTs was evaluated by comparison with a same-day rCT, using mean absolute error (MAE), mean error (ME), Dice similarity coefficient (DSC), structural non-uniformity (SNU) and signal/contrast-to-noise ratios (SNR/CNR) as metrics. Dosimetric accuracy was investigated in an intracranial setting by performing gamma analysis and calculating range shifts. Neural network-based sCTs resulted in the lowest MAE and ME (37/2 HU) and the highest DSC (0.96). While DIR and AIC generated images with a MAE of 44/77 HU, a ME of -8/1 HU and a DSC of 0.94/0.90. Gamma and range shift analysis showed almost no dosimetric difference between DCNN and DIR based sCTs. The lower image quality of AIC based sCTs affected dosimetric accuracy and resulted in lower pass ratios and higher range shifts. Patient-specific differences highlighted the advantages and disadvantages of each method. For the set of patients, the DCNN created synthetic CTs with the highest image quality. Accurate proton dose calculations were achieved by both DCNN and DIR based sCTs. The AIC method resulted in lower image quality and dose calculation accuracy was reduced compared to the other methods

Extreme leg motion analysis of professional ballet dancers via MRI segmentation of multiple leg postures

Purpose: Professional ballet dancers are subject to constant extreme motion which is known to be at the origin of many articular disorders. To analyze their extreme motion, we exploit a unique magnetic resonance imaging (MRI) protocol, denoted as ‘dual-posture' MRI, which scans the subject in both the normal (supine) and extreme (split) postures. However, due to inhomogeneous tissue intensities and image artifacts in these scans, coupled with unique acquisition protocol (split posture), segmentation of these scans is difficult. We present a novel algorithm that exploits the correlation between scans (bone shape invariance, appearance similarity) in automatically segmenting the dancer MRI images. Methods: While validated segmentation algorithms are available for standard supine MRI, these algorithms cannot be applied to the split scan which exhibits a unique posture and strong inter-subject variations. In this study, the supine MRI is segmented with a deformable models method. The appearance and shape of the segmented supine models are then re-used to segment the split MRI of the same subject. Models are first registered to the split image using a novel constrained global optimization, before being refined with the deformable models technique. Results: Experiments with 10 dual-posture MRI datasets in the segmentation of left and right femur bones reported accurate and robust results (mean distance error: 1.39 ± 0.31mm). Conclusions: The use of segmented models from the supine posture to assist the split posture segmentation was found to be equally accurate and consistent to supine results. Our results suggest that dual-posture MRI can be efficiently and robustly segmente

Spatial intensity prior correction for tissue segmentation in the developing human brain

pre-printThe degree of white matter (WM) myelination is rather inhomogeneous across the brain. As a consequence, white matter appears differently across the cortical lobes in MR images acquired during early postnatal development. At 1 year old specifically, the gray/white matter contrast of MR images in prefrontal and temporal lobes is limited and thus tissue segmentation results show commonly reduce accuracy in these lobes. In this novel work, we propose the use of spatial intensity growth maps (IGM) for T1 and T2 weighted image to compensate for local appearance inhomogeneity. The IGM captures expected intensity changes from 1 to 2 years of age, as appearance inhomogeneity is highly reduced by the age of 24 months. For that purpose, we employ MRI data from a large dataset of longitudinal (12 and 24 month old subjects) MR study of Autism. The IGM creation is based on automatically co-registered images at 12 months, corresponding registered 24 months images, and a final registration of all image to a prior average template. In template space, voxelwise correspondence is thus achieved and the IGM is computed as the coefficient of a voxelwise linear regression model between corresponding intensities at 1-year and 2-years. The proposed IGM shows low regression values of 1-10% in GM and CSF regions, as well as in WM regions at advanced stage of myelination at 1-year. However, in the prefrontal and temporal lobe we observed regression values of 20-25%, indicating that the IGM appropriately captures the expected large intensity change in these lobes due to myelination.The IGM is applied to cross-sectional MRI datasets of 1-year old subjects via registration, correction and tissue segmentation of the corrected dataset. We validated our approach in a small study of images with known, manual "ground truth" segmentations. We furthermore present an EM-like optimization of adapting existing non-optimal prior atlas probability maps to fit known expert rater segmentations

Cortical Surface Reconstruction from High-Resolution MR Brain Images

Reconstruction of the cerebral cortex from magnetic resonance (MR) images is an important step in quantitative analysis of the human brain structure, for example, in sulcal morphometry and in studies of cortical thickness. Existing cortical reconstruction approaches are typically optimized for standard resolution (~1 mm) data and are not directly applicable to higher resolution images. A new PDE-based method is presented for the automated cortical reconstruction that is computationally efficient and scales well with grid resolution, and thus is particularly suitable for high-resolution MR images with submillimeter voxel size. The method uses a mathematical model of a field in an inhomogeneous dielectric. This field mapping, similarly to a Laplacian mapping, has nice laminar properties in the cortical layer, and helps to identify the unresolved boundaries between cortical banks in narrow sulci. The pial cortical surface is reconstructed by advection along the field gradient as a geometric deformable model constrained by topology-preserving level set approach. The method's performance is illustrated on exvivo images with 0.25–0.35 mm isotropic voxels. The method is further evaluated by cross-comparison with results of the FreeSurfer software on standard resolution data sets from the OASIS database featuring pairs of repeated scans for 20 healthy young subjects

Modified mass-spring system for physically based deformation modeling

Mass-spring systems are considered the simplest and most intuitive of all deformable models. They are computationally efficient, and can handle large deformations with ease. But they suffer several intrinsic limitations. In this book a modified mass-spring system for physically based deformation modeling that addresses the limitations and solves them elegantly is presented. Several implementations in modeling breast mechanics, heart mechanics and for elastic images registration are presented

Assessment of the dosimetric accuracies of CATPhan 504 and CIRS 062 using kV-CBCT for performing direct calculations

The dosimetric accuracies of CATPhan 504 and CIRS 062 have been evaluated using the kV-CBCT of Varian TrueBeam linac and Eclipse TPS. The assessment was done using the kV-CBCT as a standalone tool for dosimetric calculations towards Adaptive replanning. Dosimetric calculations were made without altering the HU-ED curves of the planning computed tomography (CT) scanner that is used by the Eclipse TPS. All computations were done using the images and dataset from kV-CBCT while maintaining the HU-ED calibration curve of the planning CT (pCT), assuming pCT was used for the initial treatment plan. Results showed that the CIRS phantom produces doses within ±5% of the CT-based plan while CATPhan 504 produces a variation of ±14% of the CT-based plan

Modified mass-spring system for physically based deformation modeling

Mass-spring systems are considered the simplest and most intuitive of all deformable models. They are computationally efficient, and can handle large deformations with ease. But they suffer several intrinsic limitations. In this book a modified mass-spring system for physically based deformation modeling that addresses the limitations and solves them elegantly is presented. Several implementations in modeling breast mechanics, heart mechanics and for elastic images registration are presented

GIFTed Demons: deformable image registration with local structure-preserving regularization using supervoxels for liver applications.

Deformable image registration, a key component of motion correction in medical imaging, needs to be efficient and provides plausible spatial transformations that reliably approximate biological aspects of complex human organ motion. Standard approaches, such as Demons registration, mostly use Gaussian regularization for organ motion, which, though computationally efficient, rule out their application to intrinsically more complex organ motions, such as sliding interfaces. We propose regularization of motion based on supervoxels, which provides an integrated discontinuity preserving prior for motions, such as sliding. More precisely, we replace Gaussian smoothing by fast, structure-preserving, guided filtering to provide efficient, locally adaptive regularization of the estimated displacement field. We illustrate the approach by applying it to estimate sliding motions at lung and liver interfaces on challenging four-dimensional computed tomography (CT) and dynamic contrast-enhanced magnetic resonance imaging datasets. The results show that guided filter-based regularization improves the accuracy of lung and liver motion correction as compared to Gaussian smoothing. Furthermore, our framework achieves state-of-the-art results on a publicly available CT liver dataset