Tina Ehtiati

A novel method of 3D image analysis of high-resolution cone beam CT and multi slice CT for the detection of semicircular canal dehiscence.

Hypothesis We investigated if current-generation computed tomographic (CT) scanners have the resolution required to objectively detect bone structure defects as small as 0.1 mm. In addition, we propose that our method is able to predict a possible dehiscence in a semicircular canal. Background In semicircular canal dehiscence (SCD), the bone overlying the superior canal (SC) is partially absent, causing vertigo, autophony, hyperacusis or hearing loss. Diagnosis of SCD is typically based on multi-slice computed tomography (MSCT) images combined with the consideration of clinical signs and symptoms. Recent studies have shown that MSCT tends to overestimate the size of dehiscences and may skew the diagnosis towards dehiscence when a thin bone layer remains. Evaluations of CT scans for clinical application are typically observer based. Methods We developed a method of objectively evaluating the resolution of CT scanners. We did this for 2 types of computed tomography: MSCT, and cone beam computed tomography (CBCT), which have been reported to have a higher resolution for temporal bone scans. For the evaluation and comparison of image accuracy between different CT scanners and protocols, we built a bone cement phantom containing small, well-defined structural defects (diameter, 0.1–0.4 mm). These small inhomogeneities could reliably be detected by comparing the variances of radiodensities of a region of interest (i.e., a region containing a hole) with a homogenous region. The Fligner-Killeen test was used to predict the presence or absence of a hole (p ≥ 0.05). For our second goal, that is, to see how this technique could be applied to the detection of a possible dehiscence in a SC, a cadaveric head specimen was used to create an anatomic model for a borderline SCD; the SC was drilled to the point of translucency. After semi-automatically fitting the location of the canal, our variance-based approach allowed a clear, significant detection of the thin remaining bone layer. Results Our approach of statistical noise analysis on bone cement phantoms allowed us to distinguish real irregularities from measured image noise or reconstruction errors. We have shown that with computed tomography, an approach comparing radiodensity variance in regions of interest is capable of detecting inhomogeneities down to 0.1 mm (p ⩽ 0.0001). Conclusion Our analysis of data from the cadaveric head specimen demonstrates that this approach can be used to objectively detect thin layers of bone overlying an SC. This should provide the basis for using this approach for a semi-automated, objective detection of SCD.

Fused X-ray and MR Imaging Guidance of Intrapericardial Delivery of Microencapsulated Human Mesenchymal Stem Cells in Immunocompetent Swine

PURPOSE To assess intrapericardial delivery of microencapsulated, xenogeneic human mesenchymal stem cells (hMSCs) by using x-ray fused with magnetic resonance (MR) imaging (x-ray/MR imaging) guidance as a potential treatment for ischemic cardiovascular disease in an immunocompetent swine model. MATERIALS AND METHODS All animal experiments were approved by the institutional animal care and use committee. Stem cell microencapsulation was performed by using a modified alginate-poly-l-lysine-alginate encapsulation method to include 10% (wt/vol) barium sulfate to create barium-alginate microcapsules (BaCaps) that contained hMSCs. With x-ray/MR imaging guidance, eight female pigs (approximately 25 kg) were randomized to receive either BaCaps with hMSCs, empty BaCaps, naked hMSCs, or saline by using a percutaneous subxiphoid approach and were compared with animals that received empty BaCaps (n = 1) or BaCaps with hMSCs (n = 2) by using standard fluoroscopic delivery only. MR images and C-arm computed tomographic (CT) images were acquired before injection and 1 week after delivery. Animals were sacrificed immediately or at 1 week for histopathologic validation. Cardiac function between baseline and 1 week after delivery was evaluated by using a paired Student t test. RESULTS hMSCs remained highly viable (94.8% ± 6) 2 days after encapsulation in vitro. With x-ray/MR imaging, successful intrapericardial access and delivery were achieved in all animals. BaCaps were visible fluoroscopically and at C-arm CT immediately and 1 week after delivery. Whereas BaCaps were free floating immediately after delivery, they consolidated into a pseudoepicardial tissue patch at 1 week, with hMSCs remaining highly viable within BaCaps; naked hMSCs were poorly retained. Follow-up imaging 1 week after x-ray/MR imaging-guided intrapericardial delivery showed no evidence of pericardial adhesion and/or effusion or adverse effect on cardiac function. In contradistinction, BaCaps delivery with x-ray fluoroscopy without x-ray/MR imaging (n = 3) resulted in pericardial adhesions and poor hMSC viability after 1 week. CONCLUSION Intrapericardial delivery of BaCaps with hMSCs leads to high cell retention and survival. With x-ray/MR imaging guidance, intrapericardial delivery can be performed safely in the absence of preexisting pericardial effusion to provide a novel route for cardiac cellular regenerative therapy.

Planning Evaluation of C-Arm Cone Beam CT Angiography for Target Delineation in Stereotactic Radiation Surgery of Brain Arteriovenous Malformations

PURPOSE Stereotactic radiation surgery (SRS) is one of the therapeutic modalities currently available to treat cerebral arteriovenous malformations (AVM). Conventionally, magnetic resonance imaging (MRI) and MR angiography (MRA) and digital subtraction angiography (DSA) are used in combination to identify the target volume for SRS treatment. The purpose of this study was to evaluate the use of C-arm cone beam computed tomography (CBCT) in the treatment planning of SRS for cerebral AVMs. METHODS AND MATERIALS Sixteen consecutive patients treated for brain AVMs at our institution were included in this retrospective study. Prior to treatment, all patients underwent MRA, DSA, and C-arm CBCT. All images were coregistered using the GammaPlan planning system. AVM regions were delineated independently by 2 physicians using either C-arm CBCT or MRA, resulting in 2 volumes: a CBCT volume (VCBCT) and an MRA volume (VMRA). SRS plans were generated based on the delineated regions. RESULTS The average volume of treatment targets delineated using C-arm CBCT and MRA were similar, 6.40 cm(3) and 6.98 cm(3), respectively (P=.82). However, significant regions of nonoverlap existed. On average, the overlap of the MRA with the C-arm CBCT was only 52.8% of the total volume. In most cases, radiation plans based on VMRA did not provide adequate dose to the region identified on C-arm CBCT; the mean minimum dose to VCBCT was 29.5%, whereas the intended goal was 45% (P<.001). The mean volume of normal brain receiving 12 Gy or more in C-arm CBCT-based plans was not greater than in the MRA-based plans. CONCLUSIONS Use of C-arm CBCT images significantly alters the delineated regions of AVMs for SRS planning, compared to that of MRA/MRI images. CT-based planning can be accomplished without increasing the dose to normal brain and may represent a more accurate definition of the nidus, increasing the chances for successful obliteration.

Using C-Arm X-Ray Imaging to Guide Local Reporter Probe Delivery for Tracking Stem Cell Engraftment

Poor cell survival and difficulties with visualization of cell delivery are major problems with current cell transplantation methods. To protect cells from early destruction, microencapsulation methods have been developed. The addition of a contrast agent to the microcapsule also could enable tracking by MR, ultrasound, and X-ray imaging. However, determining the cell viability within the microcapsule still remains an issue. Reporter gene imaging provides a way to determine cell viability, but delivery of the reporter probe by systemic injection may be hindered in ischemic diseases. In the present study, mesenchymal stem cells (MSCs) were transfected with triple fusion reporter gene containing red fluorescent protein, truncated thymidine kinase (SPECT/PET reporter) and firefly luciferase (bioluminescence reporter). Transfected cells were microencapsulated in either unlabeled or perfluorooctylbromide (PFOB) impregnated alginate. The addition of PFOB provided radiopacity to enable visualization of the microcapsules by X-ray imaging. Before intramuscular transplantation in rabbit thigh muscle, the microcapsules were incubated with D-luciferin, and bioluminescence imaging (BLI) was performed immediately. Twenty-four and forty-eight hours post transplantation, c-arm CT was used to target the luciferin to the X-ray-visible microcapsules for BLI cell viability assessment, rather than systemic reporter probe injections. Not only was the bioluminescent signal emission from the PFOB-encapsulated MSCs confirmed as compared to non-encapsulated, naked MSCs, but over 90% of injection sites of PFOB-encapsulated MSCs were visible on c-arm CT. The latter aided in successful targeting of the reporter probe to injection sites using conventional X-ray imaging to determine cell viability at 1-2 days post transplantation. Blind luciferin injections to the approximate location of unlabeled microcapsules resulted in successful BLI signal detection in only 18% of injections. In conclusion, reporter gene probes can be more precisely targeted using c-arm CT for in vivo transplant viability assessment, thereby avoiding large and costly systemic injections of a reporter probe.

Diagnostic quality and accuracy of low dose 3D-DSA protocols in the evaluation of intracranial aneurysms

Background 3D-DSA is the ‘gold standard’ imaging technique for the diagnosis and characterization of intracranial aneurysms. Objective To compare the image quality and accuracy of low dose 3D-DSA protocols in patients with unruptured intracranial aneurysms. Materials and methods The standard manufacturer 5 s 0.36 μGy/f protocol and one of three low dose 3D-DSA protocols (5 s 0.10 μGy/f, 5 s 0.17 μGy/f, 5 s 0.24 μGy/f) were performed in 12 patients with unruptured intracranial aneurysms. Three interventional neuroradiologists, two neurosurgeons, and two neurologists rated the image quality of all 3D reconstructions as good, acceptable, or poor. Three interventional neuroradiologists measured two dimensions of each aneurysm for all protocols. The radiation dose metric Ka,r (reference point air kerma, in mGy) was recorded for each 3D-DSA protocol. Results The standard 5 s 0.36 μGy/f protocol earned the highest average subjective rating of 2.76, followed by the 5 s 0.24 μGy/f (2.72), and 5 s 0.17 μGy/f (2.59) protocols. The ranges of differences in aneurysm measurements between the 5 s 0.24 μGy/f protocol and the standard were <0.5 mm. The median Ka,r metrics for each protocol were as follows: 5 s 0.36 μGy/f (89.0 mGy), 5 s 0.24 μGy/f (57.7 mGy), 5 s 0.17 μGy/f (45.9 mGy), and 5 s 0.10 μGy/f (27.6 mGy). Conclusions Low dose 3D-DSA protocols with preserved image quality are achievable, and can help reduce exposure of patients and operators to unnecessary radiation. The 5 s 0.24 μGy/f protocol generates one-third smaller radiation dose than the standard 5 s 0.36 μGy/f protocol without compromising diagnostic image quality or accuracy.

Reducing radiation dose while maintaining diagnostic image quality of cerebral three-dimensional digital subtraction angiography: an in vivo study in swine.

Background Three-dimensional digital subtraction angiography (3D-DSA) is a modern technique that allows for better appreciation of complex vascular lesions. This study evaluates the impact of various dose reduction strategies on 3D-DSA image quality. Methods The standard manufacturer 5 s 0.36 μGy/frame setting was modified to create lower dose 3D-DSA protocols by varying the acquisition time (5 or 3 s) and/or dose per frame (0.36, 0.24, 0.17, and 0.10 μGy/f). All protocols were evaluated in three swine. Four raters measured a segment of the external carotid artery on two-dimensional multiplanar reconstruction images. The raters were also presented with three-dimensional volume rendered images from all protocols in a blinded manner and asked to choose the superior image. A full model analysis of variance with repeated measure factors was performed to compare mean differences in measurements between protocols. Results Measurement differences between the standard and low dose protocols were not clinically significant (<0.5 mm). All raters demonstrated high inter-rater reliability. The 5 s protocols were considered as qualitatively superior to the 3 s protocols. Delivered system doses ranged from 43.8 to 6.5 mGy. The 5 s 0.10 μGy/frame protocols generated 65–68% less delivered dose compared with the 5 s 0.36 μGy/frame setting. Conclusions Low dose 3D-DSA protocols with preserved image quality are achievable, and can help reduce unnecessary radiation exposure to both patients and operators. The 5 s low dose protocols generated clinically acceptable and superior images compared with the 3 s protocols, suggesting a more important role for acquisition time than dose per frame to maintain image quality.

Intrapericardial delivery of visible microcapsules containing stem cells using xfm (x-ray fused with magnetic resonance imaging)

Previously, we have demonstrated a technique to enhance survival of transplanted cells using XFM-visible microcapsules. However, theoretical concerns exist about the induction of arrhythmias if microcapsules are delivered to the heart by transendocardial injection. Delivery of these microcapsules to the pericardial space may provide an alternative approach with less potential for arrhythmia. Pericardial approaches to the epicardium have been used for the delivery of cardioactive drugs, cardiac ablation techniques and the implantation of cardiac pacemakers. However, there are no reports involving the utilization of the pericardial space for stem cell delivery.

WE-AB-BRA-08: Correction of Patient Motion in C-Arm Cone-Beam CT Using 3D-2D Registration

PURPOSE Intraoperative C-arm cone-beam CT (CBCT) is subject to artifacts arising from patient motion during the fairly long (∼5-20 s) scan times. We present a fiducial free method to mitigate motion artifacts using 3D-2D image registration that simultaneously corrects residual errors in geometric calibration. METHODS A 3D-2D registration process was used to register each projection to DRRs computed from the 3D image by maximizing gradient orientation (GO) using the CMA-ES optimizer. The resulting rigid 6 DOF transforms were applied to the system projection matrices, and a 3D image was reconstructed via model-based image reconstruction (MBIR, which accommodates the resulting noncircular orbit). Experiments were conducted using a Zeego robotic C-arm (20 s, 200°, 496 projections) to image a head phantom undergoing various types of motion: 1) 5° lateral motion; 2) 15° lateral motion; and 3) 5° lateral motion with 10 mm periodic inferior-superior motion. Images were reconstructed using a penalized likelihood (PL) objective function, and structural similarity (SSIM) was measured for axial slices of the reconstructed images. A motion-free image was acquired using the same protocol for comparison. RESULTS There was significant improvement (p < 0.001) in the SSIM of the motion-corrected (MC) images compared to uncorrected images. The SSIM in MC-PL images was >0.99, indicating near identity to the motion-free reference. The point spread function (PSF) measured from a wire in the phantom was restored to that of the reference in each case. CONCLUSION The 3D-2D registration method provides a robust framework for mitigation of motion artifacts and is expected to hold for applications in the head, pelvis, and extremities with reasonably constrained operative setup. Further improvement can be achieved by incorporating multiple rigid components and non-rigid deformation within the framework. The method is highly parallelizable and could in principle be run with every acquisition. Research supported by National Institutes of Health Grant No. R01-EB-017226 and academic-industry partnership with Siemens Healthcare (AX Division, Forcheim, Germany).

Self-calibration of cone-beam CT geometry using 3D-2D image registration: development and application to tasked-based imaging with a robotic C-arm

Purpose: Robotic C-arm systems are capable of general noncircular orbits whose trajectories can be driven by the particular imaging task. However obtaining accurate calibrations for reconstruction in such geometries can be a challenging problem. This work proposes a method to perform a unique geometric calibration of an arbitrary C-arm orbit by registering 2D projections to a previously acquired 3D image to determine the transformation parameters representing the system geometry. Methods: Experiments involved a cone-beam CT (CBCT) bench system, a robotic C-arm, and three phantoms. A robust 3D-2D registration process was used to compute the 9 degree of freedom (DOF) transformation between each projection and an existing 3D image by maximizing normalized gradient information with a digitally reconstructed radiograph (DRR) of the 3D volume. The quality of the resulting “self-calibration” was evaluated in terms of the agreement with an established calibration method using a BB phantom as well as image quality in the resulting CBCT reconstruction. Results: The self-calibration yielded CBCT images without significant difference in spatial resolution from the standard (“true”) calibration methods (p-value >0.05 for all three phantoms), and the differences between CBCT images reconstructed using the “self” and “true” calibration methods were on the order of 10-3 mm-1. Maximum error in magnification was 3.2%, and back-projection ray placement was within 0.5 mm. Conclusion: The proposed geometric “self” calibration provides a means for 3D imaging on general noncircular orbits in CBCT systems for which a geometric calibration is either not available or not reproducible. The method forms the basis of advanced “task-based” 3D imaging methods now in development for robotic C-arms.

MRI and CT tracking of mesenchymal stem cells with novel perfluorinated alginate microcapsules

Background and objectives Stem cell therapies, although promising for treating ischemic arterial diseases, suffer from poor engraftment and the inability to noninvasively monitor and track transplanted cells in vivo. Stem cell microencapsulation in conjunction with an imaging contrast agent provides a means to prevent cell immunorejection and enable cell tracking with appropriate imaging modalities. The objective of this study was to design and evaluate a novel MRIand CT-visible, immunoprotectable alginate microcapsule containing an imaging contrast agent, perfluorooctylbromide (PFOB), for mesenchymal stem cell (MSC) delivery.