Models of ischemic stroke and aneurysm
Improving diagnostic imaging in order to facilitate accurate diagnosis, optimal patient safety and treatment outcomes.
Investigating blood flow dynamics & vessel wall integrity
We researched and developed a wide variety of in vivo, in vitro, and bench top models to address the diversity present in both academic and commercial environments and are able to provide experienced assistance in every aspect from study and protocol development to analyzing final results.
Some of the in vivo models we research and develop include:
Dr Adnan H Siddiqui, Professor in the Neurosurgery Department, Dr. Elad Levy, Professor and Chairman of the Neurosurgery Department and Dr Kenneth Snyder head the Center’s research in Neurosurgery. Together with the researchers and neurosurgery fellows they work closely with the Department of Neurosurgery in the University at Buffalo and Kaleida Health to improve current devices and advance knowledge of the development of vascular disease. This is accomplished by providing an area where clinicians can participate with researchers and industry to develop our own technology and research models investigating the origin of disease states, as well as contributing to the work of others.
A DSA image shows a clot was placed & retrieved with a stent retriever from the left MCA.
X-ray based medical imaging is a complex process which involves x-ray production, interaction of the radiation with mater, radiation detection, image formation and post processing. To reduce effects of ionization on live tissue while maintaining high image quality, medical physicists dedicate a lot of effort to optimize such x-ray systems. A part of the research in our group is focused on the development of standard radiographic phantoms and analysis methods. We developed standard phantoms equivalent to human anatomy which were used successfully to improve imaging and detectors.
Left photo: Radiographic evaluation of various contrast metrics using different views through an head equivalent views
Our group has been developing dose tracking systems (DTS) that enable precise patient dose distribution measurements for dynamic procedures including those with ROI and MAF techniques. DTS, now a product of Toshiba, won first prize as the Best New Radiology Software for 2014 in a contest sponsored by the well-known trade group AuntMinnie.com.
An age-old problem in radiographic imaging is contrast and signal to noise ratio (SNR) reduction due to Compton scattering, the most probable interaction of medical x-rays with soft tissue. We pioneered a scanning beam scatter reduction method for rapid sequence imaging and applied ROI attenuation as well; however, the most common method for scatter reduction, the convenient-to-install grid, creates grid-line structured artifacts that appear as structured noise even if it oscillates during an exposure. These structures become more significant for higher resolution detectors and so we have been developing methods to divide out the grid noise patterns.
Left photo: Example of grid artifacts in a x-ray detector (left- 7a) and correction (right-7b).
As image guided interventional procedures continue to replace invasive surgical procedures and longer patient x-ray exposure times are required, there is an urgent need to reduce patient dose without jeopardizing outcomes. We have pioneered ROI techniques to achieve this goal by preserving the best image within the ROI while reducing dose peripheral to the ROI. With recent digital imaging developments we have been able to further improve real-time ROI imaging using differential temporal filtering to reduce noise especially outside the ROI and we have even combined ROI dose reduction and high resolution MAF imaging for biplane image guidance.
Micro–Computed Tomography is based on Cone Beam Computed Tomography which is a imaging modality used in hospital CT scans or angiography units, but on a small scale with increased resolution. Theses systems are used for non destructive 3D microscopy. We build our own system where we employed our own x-ray detectors. The system has resolution of 8 microns and uses a control software and reconstruction developed by our staff. The system has been used for endovascular devices integrity study, bone structure, tumor imaging, etc.
Left photo: Micro-CT sections of explanted aneurysms treated with 2 types of Asymmetric Stent taken at 3 positions, as indicated in the schematic. Brighter dots are the nitinolstruts of the stents, white arrows indicate the soft tissue, and dotted arrows indicate the holder.
The bone is a complex tissue which regulates its mass and architecture to satisfy the structural and metabolic necessities. The bone structure the body framework and it serves as a mineral reservoir. Our Micro-CT system has been extensively used to scan bone structures. Our home built detectors provide extremely high resolution and sensitivity unmatched by current flat panel technologies. We provided vital data to research groups working in dentistry, regenerative materials, implants and ageing. In addition to raw data we developed software which can calculate various morphological parameters such as: bone surface, trabecular volume, trabecular thickness, trabecular separation number and fractal dimension.
Cone beam computed tomography (CBCT) is a medical imaging technique similar to computed tomography. The X-rays are divergent, forming a cone incident on a detector. The entire system is placed on a C-arm which can rotate around the patient. CBCT has become routine procedure in treatment planning and diagnosis cardiovascular disease. Our group uses such imaging modality on a regular basis. We have focused mostly in implementation of region of interest detectors which could be used to give high resolution volumes in a particular area. We also work on new reconstruction algorithms and acquisition to optimize the image quality while decreasing the dose delivered to the patient.
Angiography is a medical imaging technique used to visualize the blood vessels lumen. This is done by injecting a radio-opaque contrast agent, such as Iodine, into the blood vessel via a catheter and imaging using X-ray imaging. This is a diagnosis technique which uses larger x-ray exposures for a very short period of time. We have worked with industry engineers to improve the quality of the images by improving hardware, imaging devices and software. In addition, novel analysis methods were developed to estimate physiological blood flow based only on angiography.
Left photo: Digital subtraction angiography (DSA) images acquired with the standard x-ray image intensifier demonstrate no residual filling of the aneurysm.
X-ray fluoroscopy is an medical imaging modality used to obtain real-time moving images. The image acquisition rate is high to allow real time visualization of internal organ motion or two guide an intervention where an interventionalist observes the motion and the position of a device in a patient. Due to extensive use the x-ray exposure is low to avoid dose and could lead to noisy images. Our group has been involved in novel approaches to improve the image quality while decreasing the dose. This involved development of new hardware, imagers and software, some of which are implemented on clinical units.
Left video: high definition fluoroscopy of a pipeline device deployment in a simulated model.
During endovascular interventions it is necessary to have the best possible real-time image guidance especially at critical stages of the intervention but only over the region of interest of the pathology being treated. For this reason we have been developing high resolution dynamic detectors that far exceed the capabilities of current imagers. Prototypes of these Micro-Angiographic Fluoroscopy (MAF) detector systems have received laudatory acceptance by clinicians. It is expected that soon these new capabilities will become the new standard of care first in neurovascular interventions and later in pediatrics, cardiology and other applications.
Dr. Rudin was awarded an NIH RO1 Grant for "High Speed Angiography at 1000 frames per second." The grant was in the top 1 percentile and received an impact score of 19 in the first submission. The long-term goal of his project is to provide unprecedented 1000 frame per second angiography based on single- photon-counting detectors but with standard x-ray sources (a total capability presently unavailable to clinicians) to enable improved diagnostic and interventional patient care. The research team expects to rigorously test the High Speed Angiography system on patient-specific pathological phantoms to evaluate the potential impact on clinical decision making primarily in neuro-endo vascular procedures such as treatment of and predictions for ischemic stroke due to vasospasm following hemorrhagic stroke. The results of this project should lead toward future clinical testing of this new imaging concept with the capability to vastly improve vascular image-guided interventional procedures by providing clinicians, even while treating the patient, to visualize for the first time the intricate details of blood flow that can be so crucial to the determination of clinical procedure outcome. We expect that, just as our previous high-spatial-resolution-detector NIH- funded project has been translated to practice, this HSAngio project will eventually become the standard state-of-the art in diagnostic and interventional imaging as well.
Left video: simulated flow through the internal carotid artery with saccular aneurysm, shown at 1000fps
Computational Fluid Dynamics
The management of Intracranial aneurysms is challenging. Clinicians are routinely faced with the dilemma whether or not to treat the patient. Using a growing database of patient-specific aneurysms (currently over 400 cases, we have built 3 statistical aneurysm rupture status stratification models based on morphology, hemodynamics and the combination of the two categories. These rupture status prediction models are validated and demonstrated the prediction value for unruptured aneurysms.
Parametric imaging, also referred to as colored coded DSA, is done by analyzing the contrast behavior at each pixel in the image. Since the early development of DSA there were many attempts to incorporate the temporal information of the contrast propagation. Such temporal information could be used to create a blood flow parametric description over the entire imaged vasculature. Despite these attempts this imaging processing method did not become clinical reality. The delays were due to various considerations such as computational speed, flow dependence on injection technique or limited knowledge of flow parameters with the patient physiology. The computational aspect meanwhile has been addressed using advanced hardware and advanced programming techniques. The value of individual pixels is tracked in each frame and a time density curve is built. Each curve is analyzed and curve parameters are calculated at each pixel. Various matrices containing parameters such as TTP, MTT, Arrival Time etc. can be calculated and later displayed using a colored mapping convention.
Flow simulation results in different treatment strategies
Vascular phantoms are a very important tool for benchtop testing of new devices and procedure. 3D printing offers a great opportunity to create testing settings very similar to the clinical situations. Using our 3D printing facility we created a plethora of patient specific arterial geometries based on CT, MRI or CBCT from patient data. Patient data acquired using various imaging modalities is loaded into a 3D station for 3D rendering and processing. We manually select the vessel of interest and perform a dynamic vessel growing and export the geometry as 3D meshes in a Stereo-Lithographic (STL) File, which will be uploaded in a mesh manipulation software. Using this software we manipulate the model to merge outlets and support in order to make a friendly benchtop model. We created full Circle of Willis models, aneurysm models, cardiac models and aortic arch models. These models can be interconnected and attached to a pump to simulate physiological flow. We use these models to simulate ischemic stroke and treatment, aneurysm treatment and diagnosis.
Connected phantoms simulate catheter advancement from the femoral arteries to the treatment site.
One approach to treat intracranial aneurysms is to use stent-like flow diverters to create thrombogenesis conditions in the aneurysm with minimal sack manipulation. Ninety percent of IA’s occur at a bifurcation, potentially in the vicinity of smaller branches. Therefore, the devices need to be flexible for easy deliverability and porous enough to avoid adjacent arterial branches occlusion, which could cause additional strokes. One of the simple Uniform Flow Diverters (UFD) being used in restricted human cases, while effective in some sidewall IA’s, is inappropriate for usage with bifurcation aneurysms. We have been heavily involved in a research projects to investigate, develop and optimize the design of a new Asymmetric Flow Diverter (AFD), for treatment of bifurcation IA’s without the short-comings associated with current uniform flow diverting stents. The new device would consist of a low-porosity region which will cover only the aneurysm neck, to effectively divert the flow. The rest of the device will be high-porosity to reduce the chance of blockage of adjacent arteries. We treated in-vitro and in-vivo bifurcation IA’s models using the new AFDs, and studied the flow changes in the aneurysm dome and in the adjacent branches.
Left photo: A−C, Self-expanding Asymmetric Flow Diverter devices. Upper: Photographs of the 3 types of these stents. Lower: Angiograms showing deployment of types A and B. Type A contains a sleeve (PTFE patch) approximately 4–5 mm wide covering the central part of the stent; types B and C have a patch covering only a given stent region. Types A and B have a closed-cell structure, whereas type C has an open-cell structure. In the photographs, black arrows indicate the platinum markers used to guide the stents during the procedure and dotted arrows indicate the marker position not visible in photographs.
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