Stephen R. Aylward

3D Slicer as an image computing platform for the Quantitative Imaging Network

Quantitative analysis has tremendous but mostly unrealized potential in healthcare to support objective and accurate interpretation of the clinical imaging. In 2008, the National Cancer Institute began building the Quantitative Imaging Network (QIN) initiative with the goal of advancing quantitative imaging in the context of personalized therapy and evaluation of treatment response. Computerized analysis is an important component contributing to reproducibility and efficiency of the quantitative imaging techniques. The success of quantitative imaging is contingent on robust analysis methods and software tools to bring these methods from bench to bedside. 3D Slicer is a free open-source software application for medical image computing. As a clinical research tool, 3D Slicer is similar to a radiology workstation that supports versatile visualizations but also provides advanced functionality such as automated segmentation and registration for a variety of application domains. Unlike a typical radiology workstation, 3D Slicer is free and is not tied to specific hardware. As a programming platform, 3D Slicer facilitates translation and evaluation of the new quantitative methods by allowing the biomedical researcher to focus on the implementation of the algorithm and providing abstractions for the common tasks of data communication, visualization and user interface development. Compared to other tools that provide aspects of this functionality, 3D Slicer is fully open source and can be readily extended and redistributed. In addition, 3D Slicer is designed to facilitate the development of new functionality in the form of 3D Slicer extensions. In this paper, we present an overview of 3D Slicer as a platform for prototyping, development and evaluation of image analysis tools for clinical research applications. To illustrate the utility of the platform in the scope of QIN, we discuss several use cases of 3D Slicer by the existing QIN teams, and we elaborate on the future directions that can further facilitate development and validation of imaging biomarkers using 3D Slicer.

The Image-Guided Surgery Toolkit IGSTK: An Open Source C++ Software Toolkit

This paper presents an overview of the image-guided surgery toolkit (IGSTK). IGSTK is an open source C++ software library that provides the basic components needed to develop image-guided surgery applications. It is intended for fast prototyping and development of image-guided surgery applications. The toolkit was developed through a collaboration between academic and industry partners. Because IGSTK was designed for safety-critical applications, the development team has adopted lightweight software processes that emphasizes safety and robustness while, at the same time, supporting geographically separated developers. A software process that is philosophically similar to agile software methods was adopted emphasizing iterative, incremental, and test-driven development principles. The guiding principle in the architecture design of IGSTK is patient safety. The IGSTK team implemented a component-based architecture and used state machine software design methodologies to improve the reliability and safety of the components. Every IGSTK component has a well-defined set of features that are governed by state machines. The state machine ensures that the component is always in a valid state and that all state transitions are valid and meaningful. Realizing that the continued success and viability of an open source toolkit depends on a strong user community, the IGSTK team is following several key strategies to build an active user community. These include maintaining a users and developers’ mailing list, providing documentation (application programming interface reference document and book), presenting demonstration applications, and delivering tutorial sessions at relevant scientific conferences.

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction☆

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the communitys attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome.

Mapping Microvasculature with Acoustic Angiography Yields Quantifiable Differences between Healthy and Tumor-bearing Tissue Volumes in a Rodent Model

PURPOSE To determine if the morphologies of microvessels could be extracted from contrast material-enhanced acoustic angiographic ultrasonographic (US) images and used as a quantitative basis for distinguishing healthy from diseased tissue. MATERIALS AND METHODS All studies were institutional animal care and use committee approved. Three-dimensional contrast-enhanced acoustic angiographic images were acquired in both healthy (n = 7) and tumor-bearing (n = 10) rats. High-spatial-resolution and high signal-to-noise acquisition was enabled by using a prototype dual-frequency US transducer (transmit at 4 MHz, receive at 30 MHz). A segmentation algorithm was utilized to extract microvessel structure from image data, and the distance metric (DM) and the sum of angles metric (SOAM), designed to distinguish different types of tortuosity, were applied to image data. The vessel populations extracted from tumor-bearing tissue volumes were compared against vessels extracted from tissue volumes in the same anatomic location within healthy control animals by using the two-sided Student t test. RESULTS Metrics of microvascular tortuosity were significantly higher in the tumor population. The average DM of the tumor population (1.34 ± 0.40 [standard deviation]) was 23.76% higher than that of the control population (1.08 ± 0.08) (P < .0001), while the average SOAM (22.53 ± 7.82) was 50.73% higher than that of the control population (14.95 ± 4.83) (P < .0001). The DM and SOAM metrics for the control and tumor populations were significantly different when all vessels were pooled between the two animal populations. In addition, each animal in the tumor population had significantly different DM and SOAM metrics relative to the control population (P < .05 for all; P value ranges for DM, 3.89 × 10(-)(7) to 5.63 × 10(-)(3); and those for SOAM, 2.42 × 10(-)(12) to 1.57 × 10(-)(3)). CONCLUSION Vascular network quantification by using high-spatial-resolution acoustic angiographic images is feasible. Data suggest that the angiogenic processes associated with tumor development in the models studied result in higher instances of vessel tortuosity near the tumor site.

IGSTK: an open source software toolkit for image-guided surgery

Image-guided surgery applies leading-edge technology and clinical practices to provide better quality of life to patients who can benefit from minimally invasive procedures. Reliable software is a critical component of image-guided surgical applications, yet costly expertise and technology infrastructure barriers hamper current research and commercialization efforts in this area. IGSTK applies the open source development and delivery model to this problem. Agile and component-based software engineering principles reduce the costs and risks associated with adopting this new technology, resulting in a safe, inexpensive, robust, shareable, and reusable software infrastructure.

3D/2D model-to-image registration applied to TIPS surgery

We have developed a novel model-to-image registration technique which aligns a 3-dimensional model of vasculature with two semiorthogonal fluoroscopic projections. Our vascular registration method is used to intra-operatively initialize the alignment of a catheter and a preoperative vascular model in the context of image-guided TIPS (Transjugular, Intrahepatic, Portosystemic Shunt formation) surgery. Registration optimization is driven by the intensity information from the projection pairs at sample points along the centerlines of the model. Our algorithm shows speed, accuracy and consistency given clinical data.

Quantification of Microvascular Tortuosity during Tumor Evolution Using Acoustic Angiography

The recent design of ultra-broadband, multifrequency ultrasound transducers has enabled high-sensitivity, high-resolution contrast imaging, with very efficient suppression of tissue background using a technique called acoustic angiography. Here we perform the first application of acoustic angiography to evolving tumors in mice predisposed to develop mammary carcinoma, with the intent of visualizing and quantifying angiogenesis progression associated with tumor growth. Metrics compared include vascular density and two measures of vessel tortuosity quantified from segmentations of vessels traversing and surrounding 24 tumors and abdominal vessels from control mice. Quantitative morphologic analysis of tumor vessels revealed significantly increased vascular tortuosity abnormalities associated with tumor growth, with the distance metric elevated approximately 14% and the sum of angles metric increased 60% in tumor vessels versus controls. Future applications of this imaging approach may provide clinicians with a new tool in tumor detection, differentiation or evaluation, though with limited depth of penetration using the current configuration.

Using Taguchi's method of experimental design to control errors in layered perceptrons

A significant problem in the design and construction of an artificial neural network for function approximation is limiting the magnitude and the variance of errors when the network is used in the field. Network errors can occur when the training data does not faithfully represent the required function due to noise or low sampling rates, when the networks flexibility does not match the variability of the data, or when the input data to the resultant network is noisy. This paper reports on several experiments whose purpose was to rank the relative significance of these error sources and thereby find neural network design principles for limiting the magnitude and variance of network errors.

The effects of healthy aging on intracerebral blood vessels visualized by magnetic resonance angiography

Histological and magnetic resonance imaging studies have demonstrated that age-associated alterations of the human brain may be at least partially related to vascular alterations. Relatively little information has been published on vascular changes associated with healthy aging, however. The study presented in this paper examined vessels segmented from standardized, high-resolution, magnetic resonance angiograms (MRAs) of 100 healthy volunteers (50 males, 50 females), aged 18-74, without hypertension or other disease likely to affect the vasculature. The subject sample was divided into 5 age groups (n=20/group) with gender equally distributed per group. The anterior cerebral, both middle cerebral, and the posterior circulations were examined for vessel number, vessel radius, and vessel tortuosity. Males exhibited larger vessel radii regardless of age and across all anatomical regions. Both males and females displayed a lower number of MRA-discernible vessels with age, most marked in the posterior circulation. Age-associated tortuosity increases were relatively mild. Our multi-modal image database has been made publicly available for use by other investigators.

A Locally Adaptive Regularization Based on Anisotropic Diffusion for Deformable Image Registration of Sliding Organs

We propose a deformable image registration algorithm that uses anisotropic smoothing for regularization to find correspondences between images of sliding organs. In particular, we apply the method for respiratory motion estimation in longitudinal thoracic and abdominal computed tomography scans. The algorithm uses locally adaptive diffusion tensors to determine the direction and magnitude with which to smooth the components of the displacement field that are normal and tangential to an expected sliding boundary. Validation was performed using synthetic, phantom, and 14 clinical datasets, including the publicly available DIR-Lab dataset. We show that motion discontinuities caused by sliding can be effectively recovered, unlike conventional regularizations that enforce globally smooth motion. In the clinical datasets, target registration error showed improved accuracy for lung landmarks compared to the diffusive regularization. We also present a generalization of our algorithm to other sliding geometries, including sliding tubes (e.g., needles sliding through tissue, or contrast agent flowing through a vessel). Potential clinical applications of this method include longitudinal change detection and radiotherapy for lung or abdominal tumours, especially those near the chest or abdominal wall.