Short-term repeatability and long-term reproducibility of quantitative MR imaging biomarkers in a single centre longitudinal study.

Quantitative imaging biomarkers (QIBs) can be defined as objective measures that are sensitive and specific to changes in tissue physiology. Provided the acquired QIBs are not affected by scanner changes, they could play an important role in disease diagnosis, prognosis, management, and treatment monitoring. The precision of selected QIBs was assessed from data collected on a 3-T scanner in four healthy participants over a 5-year period. Inevitable scanner changes and acquisition protocol revisions occurred during this time. Standard and custom processing pipelines were used to calculate regional brain volume, cortical thickness, T2, T2*, quantitative susceptibility, cerebral blood flow, axial, radial and mean diffusivity, peak width of skeletonized mean diffusivity, and fractional anisotropy from the acquired images. Coefficient of variation (CoV) and intra-class correlation (ICC) indices were determined in the short-term (i.e., repeatable over three acquisitions within 4 weeks) and in the long-term (i.e., reproducible over four acquisition sessions in 5 years). Precision indices varied based on acquisition technique, processing pipeline, and anatomical region. Good repeatability (average CoV=2.40% and ICC=0.78) and reproducibility (average CoV=8.86 % and ICC=0.72) were found over all QIBs. The best performance indices were obtained for diffusion derived biomarkers (CoV∼0.96% and ICCs=0.87); conversely, the poorest indices were found for the cerebral blood flow biomarker (CoV>10% and ICC<0.5). These results demonstrate that changes in protocol, along with hardware and software upgrades, did not affect the estimates of the selected biomarkers and their precision. Further characterization of the QIB is necessary to understand meaningful changes in the biomarkers in longitudinal studies of normal brain aging and translation to clinical research.

SimITK: visual programming of the ITK image-processing library within Simulink.

The Insight Segmentation and Registration Toolkit (ITK) is a software library used for image analysis, visualization, and image-guided surgery applications. ITK is a collection of C++ classes that poses the challenge of a steep learning curve should the user not have appropriate C++ programming experience. To remove the programming complexities and facilitate rapid prototyping, an implementation of ITK within a higher-level visual programming environment is presented: SimITK. ITK functionalities are automatically wrapped into "blocks" within Simulink, the visual programming environment of MATLAB, where these blocks can be connected to form workflows: visual schematics that closely represent the structure of a C++ program. The heavily templated C++ nature of ITK does not facilitate direct interaction between Simulink and ITK; an intermediary is required to convert respective data types and allow intercommunication. As such, a SimITK "Virtual Block" has been developed that serves as a wrapper around an ITK class which is capable of resolving the ITK data types to native Simulink data types. Part of the challenge surrounding this implementation involves automatically capturing and storing the pertinent class information that need to be refined from an initial state prior to being reflected within the final block representation. The primary result from the SimITK wrapping procedure is multiple Simulink block libraries. From these libraries, blocks are selected and interconnected to demonstrate two examples: a 3D segmentation workflow and a 3D multimodal registration workflow. Compared to their pure-code equivalents, the workflows highlight ITK usability through an alternative visual interpretation of the code that abstracts away potentially confusing technicalities.

Brain iron content in cerebral amyloid angiopathy using quantitative susceptibility mapping.

Introduction: Cerebral amyloid angiopathy (CAA) is a small vessel disease that causes covert and symptomatic brain hemorrhaging. We hypothesized that persons with CAA would have increased brain iron content detectable by quantitative susceptibility mapping (QSM) on magnetic resonance imaging (MRI), and that higher iron content would be associated with worse cognition. Methods: Participants with CAA (n = 21), mild Alzheimer's disease with dementia (AD-dementia; n = 14), and normal controls (NC; n = 83) underwent 3T MRI. Post-processing QSM techniques were applied to obtain susceptibility values for regions of the frontal and occipital lobe, thalamus, caudate, putamen, pallidum, and hippocampus. Linear regression was used to examine differences between groups, and associations with global cognition, controlling for multiple comparisons using the false discovery rate method. Results: No differences were found between regions of interest in CAA compared to NC. In AD, the calcarine sulcus had greater iron than NC (ß = 0.99 [95% CI: 0.44, 1.53], q < 0.01). However, calcarine sulcus iron content was not associated with global cognition, measured by the Montreal Cognitive Assessment (p > 0.05 for all participants, NC, CAA, and AD). Discussion: After correcting for multiple comparisons, brain iron content, measured via QSM, was not elevated in CAA compared to NC in this exploratory study.

Tactics: an open-source platform for planning, simulating and validating stereotactic surgery.

Frame-based stereotaxy is widely used for planning and implanting deep-brain electrodes. In 2013, as part of a clinical study on deep-brain stimulation for treatment-resistant depression, our group identified a need for software to simulate and plan stereotactic procedures. Shortcomings in extant commercial systems encouraged us to develop Tactics. Tactics is purpose-designed for frame-based stereotactic placement of electrodes. The workflow is far simpler than commercial systems. By simulating specific electrode placement, immediate in-context view of each electrode contact, and the cortical entry site are available within seconds. Post implantation, electrode placement is verified by linearly registering post-operative images. Tactics has been particularly helpful for invasive electroencephalography electrodes where as many as 20 electrodes are planned and placed within minutes. Currently, no commercial system has a workflow supporting the efficient placement of this many electrodes. Tactics includes a novel implementation of automated frame localization and a user-extensible mechanism for importing electrode specifications for visualization of individual electrode contacts. The system was systematically validated, through comparison against gold-standard techniques and quantitative analysis of targeting accuracy using a purpose-built imaging phantom mountable by a stereotactic frame. Internal to our research group, Tactics has been used to plan over 300 depth-electrode targets and trajectories in over 50 surgical cases, and to plan dozens of stereotactic biopsies. Source code and pre-built binaries for Tactics are public and open-source, enabling use and contribution by the extended community.

Automatic fusion of freehand endoscopic brain images to three-dimensional surfaces: creating stereoscopic panoramas.

A major limitation of the use of endoscopes in minimally invasive surgery is the lack of relative context between the endoscope and its surroundings. The purpose of this work was to fuse images obtained from a tracked endoscope to surfaces derived from three-dimensional (3-D) preoperative magnetic resonance or computed tomography (CT) data, for assistance in surgical planning, training and guidance. We extracted polygonal surfaces from preoperative CT images of a standard brain phantom and digitized endoscopic video images from a tracked neuro-endoscope. The optical properties of the endoscope were characterized using a simple calibration procedure. Registration of the phantom (physical space) and CT images (preoperative image space) was accomplished using fiducial markers that could be identified both on the phantom and within the images. The endoscopic images were corrected for radial lens distortion and then mapped onto the extracted surfaces via a two-dimensional 2-D to 3-D mapping algorithm. The optical tracker has an accuracy of about 0.3 mm at its centroid, which allows the endoscope tip to be localized to within 1.0 mm. The mapping operation allows multiple endoscopic images to be "painted" onto the 3-D brain surfaces, as they are acquired, in the correct anatomical position. This allows panoramic and stereoscopic visualization, as well as navigation of the 3-D surface, painted with multiple endoscopic views, from arbitrary perspectives.

Generalized 3D nonlinear transformations for medical imaging: an object-oriented implementation in VTK.

We have contributed an efficient, object-oriented implementation of 3D nonlinear transformations to the Visualization Toolkit that can be applied to a wide variety of data types, including images and polygonal meshes. The transformations are performed via thin-plate splines or via interpolation of a regular lattice of displacement vectors, and are part of a framework that is easily extensible to other nonlinear transformation types. In this paper we demonstrate application of these transformations in medical imaging in general and image-guided surgery in particular, and present a series of performance benchmarks.

Integrated navigation and control software system for MRI-guided robotic prostate interventions.

A software system to provide intuitive navigation for MRI-guided robotic transperineal prostate therapy is presented. In the system, the robot control unit, the MRI scanner, and the open-source navigation software are connected together via Ethernet to exchange commands, coordinates, and images using an open network communication protocol, OpenIGTLink. The system has six states called "workphases" that provide the necessary synchronization of all components during each stage of the clinical workflow, and the user interface guides the operator linearly through these workphases. On top of this framework, the software provides the following features for needle guidance: interactive target planning; 3D image visualization with current needle position; treatment monitoring through real-time MR images of needle trajectories in the prostate. These features are supported by calibration of robot and image coordinates by fiducial-based registration. Performance tests show that the registration error of the system was 2.6mm within the prostate volume. Registered real-time 2D images were displayed 1.97 s after the image location is specified.

Quantification of edematic effects in prostate brachytherapy interventions.

We present a quantitative model to analyze the detrimental effects of for edema on the quality of prostate brachytherapy implants We account for both tissue expansion and implant migration by mapping intra-operative ultrasound and post-implant CT. We pre-process the ultrasound with a phase congruency filter, and map it to the volume CT using a B-spline deformable mutual information similarity metric. To test the method, we implanted a standard training phantom with 48 seeds, imaged the phantom with ultrasound and CT and registered the two for ground truth. Edema was simulated by distorting the CT volume by known transformations. The objective was to match the distorted implant to the intra-operative ultrasound. Performance was measured relative to ground truth. We successfully mapped 100% of deformed seeds to ground truth under edematic expansion up to 40% of volume growth. Seed matching performance was 98% with random seed migration of 3mm superimposed on 10% edematic volume growth. This method promises to be clinically applicable as the first quantitative analysis tool to measure edematic implant deformations occurring between the operating room and post-operative CT imaging.

Software strategy for robotic transperineal prostate therapy in closed-bore MRI.

A software strategy to provide intuitive navigation for MRI-guided robotic transperineal prostate therapy is presented. In the system, the robot control unit, the MRI scanner, and open-source navigation software are connected to one another via Ethernet to exchange commands, coordinates, and images. Six states of the system called "workphases" are defined based on the clinical scenario to synchronize behaviors of all components. The wizard-style user interface allows easy following of the clinical workflow. On top of this framework, the software provides features for intuitive needle guidance: interactive target planning; 3D image visualization with current needle position; treatment monitoring through real-time MRI. These features are supported by calibration of robot and image coordinates by the fiducial-based registration. The performance test shows that the registration error of the system was 2.6 mm in the prostate area, and it displayed real-time 2D image 1.7 s after the completion of image acquisition.