The authors would like to thank the Ulm University Center for Translational Imaging MoMAN for its support.

The study protocol is in compliance with the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution&#39;s ethics committee. Written informed consent was obtained from all individual participants included in the study (CSI-Ulm, clinicaltrials.gov NCT02162069).
1. CT Examination
<ol>
	<li>Perform cardiac CT angiography with retrospective ECG-gating using 80 mL of iodinated contrast media injected at a flow rate of 4.0 mL/s followed by a flushing bolus of 70 mL 0.9% saline solution.</li>
	<li>Acquire data cranio-caudally extending from the femoral arteries to the subclavian arteries with the following acquisition parameters: the matrix of 512 &#215; 512 pixels, slice thickness of 1 mm, slice spacing of 0.7 mm.</li>
	<li>Reconstruct images at 30% of the R-R interval using iterative reconstruction algorithm.</li>
</ol>
2. Image Segmentation and Model Generation
<ol>
	<li>Import CT data from an external device or an internal archiving system into image fusion software by drag-and-dropping the dataset or subsets of data for the selected patient into the Patients view within the application.</li>
	<li>Start automatic segmentation of the selected CT volume by double-clicking on the image series. 
	Note: Segmentation of the heart chambers (left and right ventricle, left and right atrium, myocardium) and great vessels (abdominal aorta, vena cava, and coronary sinus) is started automatically and will be displayed in the Segmentation work step.</li>
	<li>Go through the image slices and verify if the edges of the aorta and left ventricle are correctly detected and if necessary edit the automatic segmentation in the Tissue window using the Edit button.</li>
	<li>To perform manual segmentation of additional structures, use the Add button in the Tissue window.</li>
	<li>Use existing editing tools to fill the structure (Inject Dye) and drag the edges of the structure (Drag Edge) in 2D views or remove structure parts with the Free-form Cut in the 3D view.</li>
	<li>Perform manual segmentation of the main trunks of the left and right coronary arteries, main artery branches (brachiocephalic artery with right carotid and right subclavian arteries, left common carotid artery and left subclavian artery), left and right iliofemoral arteries, hip bones, and hip joints as described in steps 2.4-2.5 (Figure 1). 
	Note: Depending on the quality of the CT volume this may take 20 to 30 min.</li>
</ol>
3. Image Co-registration and Fusion
<ol>
	<li>In the Patients view merge the selected patient with the current patient in the XR system by choosing the respective action in the right-click-context-menu. 
	Note: Now the Registration and Live work steps are active and can be used.</li>
	<li>In the Live work step, click Add new tag point in the Tag points window to place three reference markers at aortic valve cusps for facilitating the choice of the optimal projection of the annular plane during the intervention (Figure 2).</li>
	<li>Go to the Registration work step to acquire the XR runs and to perform the co-registration of the segmented models with XR. 
	Note: XR runs acquired with at least 30&#176; angular distance are required for reliable registration.</li>
	<li>Copy the angiographic projection of the appropriate puncture in ~LAO 20 - 30&#176; orientation (or ~RAO 20 - 30&#176; depending on the initial puncture side) into the Reference view 1 by clicking the button Copy to Reference View 1.</li>
	<li>Copy following x-ray projections acquired in ~AP orientation during visualization of the transition from the contralateral A. iliaca communis to the A. femoralis communis into the Reference view 2 by clicking the button Copy to Reference View 2.</li>
	<li>Use the interaction tools Registration Pan, Registration Rotate (for in-plane rotation), Registration Roll (for 3D rotation) to manually align the model of the iliofemoral arteries with the acquired XR projections (Figure 3A-B).</li>
	<li>Use hip bones and hip joints visible in the XR images as additional landmarks during alignment of the overlay in the iliofemoral region. 
	Note: Now the model is linked to the XR system geometry, and the overlay is automatically being adapted to the current XR projection orientation, magnification, and patient table position.</li>
	<li>Guide the puncture of the common femoral artery on the sheath side (Figure 3C) by using the coarse initial co-registration performed in step 3.6.</li>
	<li>Record an angiographic projection of the device sheath femoral artery in ~RAO 20 - 30&#176; (or respectively ~LAO 20 - 30&#176;) by clicking the button Copy to Reference View and finalize the image co-registration in the iliofemoral region (Figure 3D). 
	Note: Since the patient is positioned differently during CT scan and the intervention, registration based on the iliofemoral structures provides only limited accuracy in other regions. Thus, manual refinement of the co-registration in the thoracic region is required.</li>
	<li>To use these data for further overlay re-alignment, copy any additional acquired projections to the &#8220;Reference View&#8221; during the transition from the iliofemoral to the thoracic region as well as any catheterization of the brachiocephalic trunk via the right radial artery.</li>
	<li>After placing the pigtail catheter in the aortic arch, acquire two fluoroscopic projections without CA in LAO 30 - 40&#176; and RAO 20 - 30&#176; orientation and copy them in the Reference view 1 and Reference view 2.</li>
	<li>Use the interaction tools Registration Pan, Registration Rotate (for in-plane rotation), Registration Roll (for 3D rotation) to manually adjust the registration in the thoracic region (Figure 4A-B).</li>
	<li>Guide the placement of the protection device without administration of additional CA purely based on the anatomic overlay (Figure 4C).</li>
	<li>For further refinement, manually correct the overlay position as described in step 3.12&#160;on each acquired XR projection during the entire course of the intervention, ensuring accurate overlay at any time point. 
	Note: Use aortograms acquired according to the routine procedure for verifying the correct position of the delivery system as landmarks for the overlay adjustment (Figure 4D).</li>
</ol>

<ol>
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M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fusion+of+CT+Angiography+or+MR+Angiography+with+Unenhanced+CBCT+and+Fluoroscopy+Guidance+in+Endovascular+Treatments+of+Aorto-Iliac+Steno-Occlusion:+Technical+Note+on+a+Preliminary+Experience.">Fusion of CT Angiography or MR Angiography with Unenhanced CBCT and Fluoroscopy Guidance in Endovascular Treatments of Aorto-Iliac Steno-Occlusion: Technical Note on a Preliminary Experience.</a> CardioVascular and Interventional Radiology. 39 (1), 111-116 (2015).</li><li>Sailer, A. 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R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Integration+of+MDCT+and+fluoroscopy+using+C-arm+computed+tomography+to+guide+structural+cardiac+interventions+in+the+cardiac+catheterization+laboratory.">Integration of MDCT and fluoroscopy using C-arm computed tomography to guide structural cardiac interventions in the cardiac catheterization laboratory.</a> Catheterization and Cardiovascular Interventions. 85 (1), 139-147 (2015).</li><li>Movassaghi, B., Rasche, V., Grass, M., Viergever, M. A., Niessen, W. 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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transcatheter+Aortic+Valve+Replacement+(TAVR):+Access+Planning+and+Strategies.">Transcatheter Aortic Valve Replacement (TAVR): Access Planning and Strategies.</a> Methodist DeBakey Cardiovascular Journal. 8 (2), 22-25 (2012).</li><li>W&#246;hrle, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transfemoral+Aortic+Valve+Implantation+with+the+New+Edwards+Sapien+3+Valve+for+Treatment+of+Severe+Aortic+Stenosis-Impact+of+Valve+Size+in+a+Single+Center+Experience.">Transfemoral Aortic Valve Implantation with the New Edwards Sapien 3 Valve for Treatment of Severe Aortic Stenosis-Impact of Valve Size in a Single Center Experience.</a> PLOS ONE. 11 (3), e0151247 (2016).</li><li>Seeger, J., Gonska, B., Otto, M., Rottbauer, W., W&#246;hrle, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cerebral+Embolic+Protection+During+Transcatheter+Aortic+Valve+Replacement+Significantly+Reduces+Death+and+Stroke+Compared+With+Unprotected+Procedures.">Cerebral Embolic Protection During Transcatheter Aortic Valve Replacement Significantly Reduces Death and Stroke Compared With Unprotected Procedures.</a> JACC: Cardiovascular Interventions. 10 (22), 2297-2303 (2017).</li><li>Seeger, J., Gonska, B., Rodewald, C., Rottbauer, W., W&#246;hrle, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impact+of+suture+mediated+femoral+access+site+closure+with+the+Prostar+XL+compared+to+the+ProGlide+system+on+outcome+in+transfemoral+aortic+valve+implantation.">Impact of suture mediated femoral access site closure with the Prostar XL compared to the ProGlide system on outcome in transfemoral aortic valve implantation.</a> International Journal of Cardiology. 223, 564-567 (2016).</li><li>Vernikouskaya, I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient-specific+registration+of+3D+CT+angiography+(CTA)+with+X-ray+fluoroscopy+for+image+fusion+during+transcatheter+aortic+valve+implantation+(TAVI)+increases+performance+of+the+procedure.">Patient-specific registration of 3D CT angiography (CTA) with X-ray fluoroscopy for image fusion during transcatheter aortic valve implantation (TAVI) increases performance of the procedure.</a> Clinical Research in Cardiology. , (2018).</li><li>Eng, M. H., Kim, M. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Fluoroscopy+and+CT+fusion+overlay-greater+than+the+sum+of+their+parts.">Fluoroscopy and CT fusion overlay-greater than the sum of their parts.</a> Catheterization and Cardiovascular Interventions. 85 (1), 148-149 (2015).</li><li>John, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=System+to+guide+transcatheter+aortic+valve+implantations+based+on+interventional+C-arm+CT+imaging.">System to guide transcatheter aortic valve implantations based on interventional C-arm CT imaging.</a> Medical Image Computing and Computer-Assisted Intervention. 13 (Pt 1), 375-382 (2010).</li><li>Lu, Y., Sun, Y., Liao, R., Ong, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+pre-operative+CT+and+non-contrast-enhanced+C-arm+CT+registration+framework+for+trans-catheter+aortic+valve+implantation.">A pre-operative CT and non-contrast-enhanced C-arm CT registration framework for trans-catheter aortic valve implantation.</a> Computerized Medical Imaging and Graphics. 38 (8), 683-695 (2014).</li></ol>

On behalf of all authors, the corresponding authors state that there are no relationships that could be construed as a conflict of interest.

The main focus of this study was to investigate the feasibility of IF without modifying the clinically established TAVI workflow. Whereas the gold standard for the co-registration of the pre-interventional CTA data and XR fluoroscopy uses dedicated aortograms8, we propose using multiple approximate registrations with on-the-fly refinements to provide accurate 3D model overlay during the entire course of the intervention.
The continuous manual registration refinement requires additional trained staff to assist the interventional team from the control room. The required refinements are difficult to perform at the tableside since the related user interactions impact the clinically established interventional workflow. However, even though the co-registration based on the acquisition of two dedicated aortograms is potentially easier to realize at the tableside, the 3D overlay would not be available during femoral access, and any motion of the patient would spoil the accuracy of the registration.
Even the use of static roadmaps, not considering the cardiac and respiratory motion, appeared promising for femoral puncture, placement of the embolic protection device and initial alignment of the valve prosthesis. However, the usage of cardiac phase synchronized anatomic models in combination with respiratory motion compensation may further increase the usefulness of the proposed approach by accounting for dynamic changes in the aortic annulus position, especially during the valve deployment.
3D model overlay represents another incremental advancement to improve the navigation of complex interventions leading to an improved procedural safety and efficacy14. Co-registration of the pre-interventional CT data to live fluoroscopy by means of contrast-enhanced CBCT may raise concerns regarding high XR dose and additional CA, despite its reported success6,15. Using native CBCT instead is limited by the poor visibility of the target structures and causes difficulties in registration and highly trained operators are necessary, making the workflow less straightforward6,16. Even though using two additional aortograms for the co-registration allowed for accurate co-registration, no reduction of neither CA nor XR dose could be achieved8. The proposed co-registration approach yields significant reduction of the fluoroscopy dose, contrast volume and overall procedure time while maintaining the usual workflow during the implantation. Furthermore, it already supports femoral artery puncture by superimposing respective models during the initial phase of the intervention.
The current limitation of the technique results from the static nature of the anatomical models and non-deformable rigid registration, potentially causing overlay inaccuracy. In particular, different patient positioning between pre-interventional imaging and the intervention as well as thin, tortuous structures which easily deform during device manipulation may cause a mismatch between the anatomical models and the live situation.
The proposed protocol as such is applicable to a huge variety of transcatheter interventions. With the increasing complexity of these procedures, the demand for improved guidance will steadily rise. Procedures on the verge for the clinical routine like the percutaneous treatment of the tricuspid valve as well as procedures already clinically established like atrial or ventricular ablation will likely benefit from the suggested approach. Even though the procedure is explained in terms of one specific system, the approach should be easily transferable to other systems as long as a similar software solution is available.

Image fusion (IF) is the process of superimposing datasets acquired at the different time- and viewpoints on different modalities into a single-frame of reference1. XR is the most frequently used imaging modality for intervention guidance. Even though, providing high temporal and spatial resolution, XR has low dimensionality (2D projections) and lacks anatomical details. 3D organ shape models derived from e.g. high-quality pre-interventional CTA data superimposed onto the live fluoroscopy image can augment XR by relevant anatomic soft-tissue structures. Prerequisite step for IF is the co-registration of the different imaging modalities.
Typically, co-registration of preoperative 3D image datasets with XR fluoroscopy involves one of the following techniques2: a) image-based 3D-3D registration of the preoperative 3D dataset with an intraoperative non-/contrast-enhanced CBCT dataset3,4,5,6, or b) direct image-based 2D-3D registration, where two angiographic images with a minimum of 30&#176; angular spacing7,8 are used for co-registration.
With the recent introduction of fusion packages on commercial XR systems, IF can be made more readily available for a wide range of applications. Using those systems, we have previously shown that it is technically feasible and safe to overlay an aortic root model by means of direct image-based 2D-3D registration for supporting transfemoral transcatheter aortic valve implantation (TAVI)8. Without compromising the overall CA or XR dose, IF proved itself highly valuable during TAVI procedure by adding 3D anatomical details to the conventional XR fluoroscopy image, especially during deployment of the cerebral protection device. However, the additional acquisition of the aortograms used for the co-registration required additional CA and XR dose. Therefore, an optimized workflow providing accurate IF without the need of any additional aortograms was highly desirable.
Here, we present an approach to improved co-registration of pre-interventional CTA with real-time XR without requiring any additional CA or C-arm CT scans for IF. The femoral access TAVI is performed as described elsewhere9,10,11. Briefly, both femoral arteries are accessed: one for the guidance of the contralateral puncture, followed by placement of a pigtail catheter through a 6F sheath to allow arteriography during placement of the valve prosthesis; the second for placement of the valve delivery system and subsequent balloon valvuloplasty and device placement. Angiographic confirmation of appropriate puncture is performed in our institution as a standard of care for localization of the puncture height (above the femoral bifurcation) and estimation of the position of the covered stent in case of access-related complications12. For capturing embolic debris, a double-filter cerebral protection system is introduced after insertion of the TAVI delivery sheath prior to the passage of the aortic arch with any further device.
We use arteriograms performed routinely during the puncture of the femoral arteries to establish the initial co-registration. On-the-fly refinement of the co-registration is subsequently performed during the on-going procedure using the position of the pigtail catheter within the aortic root, the double-filter cerebral embolic protection system in the supraaortal vessels and the aortograms performed before the implantation of the valve prosthesis, thus ensuring accurate model overlay at any time point during the intervention.

<table border="0" cellpadding="0" cellspacing="0" style="width:733px;" width="733">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:247px;">Philips Allura FD10&#160;&#160;</td>
			<td style="width:149px;">Philips Healthcare</td>
			<td style="width:136px;"></td>
			<td style="width:201px;">x-ray system</td>
		</tr>
		<tr height="43">
			<td height="43" style="height:43px;width:247px;">EP Navigator Release 5.2.10</td>
			<td style="width:149px;">Philips Healthcare</td>
			<td style="width:136px;"></td>
			<td style="width:201px;">image segmentation and fusion SW</td>
		</tr>
		<tr height="39">
			<td height="39" style="height:39px;width:247px;">Iomeron 350</td>
			<td style="width:149px;">Bracco Imaging Deutschland GmbH</td>
			<td style="width:136px;"></td>
			<td>x-ray contrast agent</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:41px;width:247px;">Sentinel&#160; double-filter cerebral protection system</td>
			<td style="width:149px;">Claret Medical, Inc.</td>
			<td style="width:136px;"></td>
			<td style="width:201px;">double-filter cerebral protection system&#160;</td>
		</tr>
		<tr height="27">
			<td height="27" style="height:27px;width:247px;">Matlab R2013</td>
			<td style="width:149px;">MathWorks</td>
			<td style="width:136px;"></td>
			<td>statistical analysis</td>
		</tr>
	</tbody>
</table>

improved registration of 3d ct angiography with x-ray fluoroscopy for image fusion during transcatheter aortic valve implantation

The fusion of 3D anatomical models derived from high-fidelity pre-interventional computed tomography angiography (CTA), and x-ray (XR) fluoroscopy to facilitate anatomical guidance is of huge interest for complex cardiac interventions like TAVI procedures with cerebral protection. Co-registration of CTA and XR has been introduced either based on additional intraoperative non-/contrast-enhanced cone-beam computed tomography (CBCT) or two separate aortograms. With the related increase of radiation exposure and/or contrast agent (CA) dose, a potential additional risk for the patient is introduced. Here, we propose a modified co-registration approach making use of arteriograms of the iliofemoral arteries, routinely performed during the femoral puncture and sheath introduction. On-the-fly refinement of the co-registration during the on-going procedure enables accurate co-registration without any additional angiograms, thus reducing CA, XR dose and procedure time, while simultaneously improving operator confidence and procedure safety.

We introduced a novel co-registration approach for image fusion during TAVI, which allows overlaying the patient-specific anatomic model onto the live XR images during the entire TAVI procedure without the need for any additional aortograms.
Several interventional steps will benefit from the IF: (1) guidance of the puncture of the common femoral artery above the femoral bifurcation on the sheath side (Figure 5A); (2) accurate placement of the cerebral embolic protection device even in very tortuous anatomies&#160;based solely&#160;on the anatomic overlay (Figure 5B); (3) visualization of the model in arbitrary C-arm angulation without any XR exposure and CA administration (Figure 2), as well as identification of the optimal view before the valve deployment (Figure 5C); (4) alignment of the valve prosthesis even in very complex anatomies (Figure 5D).
In the related clinical study13, the proposed IF approach could prove significant reduction of the CA volume [80 (50 - 95) vs. 100 (80 - 110) mL, p = 0.010], overall procedure time [48 (41 - 58) vs. 61 (53 - 67) min, p = 0.002] and procedure XR dose [51 (42 - 55) vs. 64 (49 - 81) Gy cm2, p = 0.032] in comparison with a matched control group.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57858/57858fig1.jpg" /> 
Figure 1: 3D models of the CTA-based segmented aortic arch with coronary, carotid and subclavian arteries (red), iliac and femoral arteries (green), left ventricle (purple), hip bones (yellow), and hip joints (blue). <a href="/files/ftp_upload/57858/57858fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/57858/57858fig2.jpg" /> 
Figure 2: Manual setting of the reference markers (blue dots) at the aortic valve cusps for facilitating the choice of the optimal projection of the annular plane. A. Oblique view. B. Orthogonal view. <a href="/files/ftp_upload/57858/57858fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/57858/57858fig3.jpg" /> 
Figure 3: Registration between the 3D model and XR system in the iliofemoral region. A. Arteriogram of the punctured non-device sheath femoral artery in LAO 20&#176;. B. Arteriogram of the iliac arteries in RAO 4&#176; orientation. C. Puncture of the vessel selected for the delivery sheath in RAO 4&#176;. D. Confirmation of the wire position inside the vessel selected for the delivery sheath in RAO 21&#176;. <a href="/files/ftp_upload/57858/57858fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/57858/57858fig4.jpg" /> 
Figure 4: Refinement of the co-registration in the thoracic region. The overlay is re-aligned based on two reference projections of the abdominal aorta after insertion of the pigtail catheter A. acquired in LAO 32&#176; and B. RAO 23&#176;. Further refinements may be done after the placement of C. the cerebral embolic protection device and D. based on the angiographic projections of the aortic annulus. <a href="/files/ftp_upload/57858/57858fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/57858/57858fig5.jpg" /> 
Figure 5: Examples of successful image fusion. A. Femoral puncture. B. Placement of the cerebral embolic protection device. C. Valve deployment (C-arm is aligned perpendicular to the annular plane as it can be seen via three markers set at the aortic annulus aligned along a straight line). D. Valve prosthesis after deployment in the aortic annulus. <a href="/files/ftp_upload/57858/57858fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Improved Registration of 3D CT Angiography with X-ray Fluoroscopy for Image Fusion During Transcatheter Aortic Valve Implantation at JoVE.com

Improved Registration of 3D CT Angiography with X-ray Fluoroscopy for Image Fusion During Transcatheter Aortic Valve Implantation

The aim of this study was to improve the co-registration for image fusion (IF) of pre-interventional CT data with real-time x-ray (XR) fluoroscopy during transfemoral transcatheter aortic valve implantation (TAVI).

The fusion of 3D anatomical models derived from high-fidelity pre-interventional computed tomography angiography (CTA), and x-ray (XR) fluoroscopy to ...

improved-registration-3d-ct-angiography-with-x-ray-fluoroscopy-for

Nanyang Technological University

Research

JoVE Journal

Medicine

10.3K Views.  Ulm University Medical Center. The aim of this study was to improve the co-registration for image fusion (IF) of pre-interventional CT data with real-time x-ray (XR) fluoroscopy during transfemoral transcatheter aortic valve implantation (TAVI).

Video: Improved Registration of 3D CT Angiography with X-ray Fluoroscopy for Image Fusion During Transcatheter Aortic Valve Implantation

Intracranial Implantation with Subsequent 3D In Vivo Bioluminescent Imaging of Murine Gliomas

The mouse glioma 261 (GL261) is recognized as an in vivo model system that recapitulates many of the features of human glioblastoma multiforme (GBM). The cell line was originally induced by intracranial injection of 3-methyl-cholantrene into a C57BL/6 syngeneic mouse strain 1; therefore, immunologically competent C57BL/6 mice can be used. While we use GL261, the following protocol can be used for the implantation and monitoring of any intracranial mouse tumor model. GL261 cells were engineered to stably express firefly luciferase (GL261-luc). We also created the brighter GL261-luc2 cell line by stable transfection of the luc2 gene expressed from the CMV promoter. C57BL/6-cBrd/cBrd/Cr mice (albino variant of C57BL/6) from the National Cancer Institute, Frederick, MD were used to eliminate the light attenuation caused by black skin and fur. With the use of albino C57BL/6 mice; in vivo imaging using the IVIS Spectrum in vivo imaging system is possible from the day of implantation (Caliper Life Sciences, Hopkinton, MA). The GL261-luc and GL261-luc2 cell lines showed the same in vivo behavior as the parental GL261 cells. Some of the shared histological features present in human GBMs and this mouse model include: tumor necrosis, pseudopalisades, neovascularization, invasion, hypercellularity, and inflammation 1.
Prior to implantation animals were anesthetized by an intraperitoneal injection of ketamine (50 mg/kg), xylazine (5 mg/kg) and buprenorphine (0.05 mg/kg), placed in a stereotactic apparatus and an incision was made with a scalpel over the cranial midline. A burrhole was made 0.1mm posterior to the bregma and 2.3mm to the right of the midline. A needle was inserted to a depth of 3mm and withdrawn 0.4mm to a depth of 2.6mm. Two &mu;l of GL261-luc or GL261-luc2 cells (107 cells/ml) were infused over the course of 3 minutes. The burrhole was closed with bonewax and the incision was sutured.
Following stereotactic implantation the bioluminescent cells are detectable from the day of implantation and the tumor can be analyzed using the 3D image reconstruction feature of the IVIS Spectrum instrument. Animals receive a subcutaneous injection of 150&mu;g luciferin /kg body weight 20 min prior to imaging. Tumor burden is quantified using mean tumor bioluminescence over time. Tumor-bearing mice were observed daily to assess morbidity and were euthanized when one or more of the following symptoms are present: lethargy, failure to ambulate, hunched posture, failure to groom, anorexia resulting in &gt;10% loss of weight. Tumors were evident in all of the animals on necropsy.

Intracranial Implantation with Subsequent 3D In Vivo Bioluminescent Imaging of Murine Gliomas

Intracranial implantation of GL261 cells into C57BL/6 mice produces malignant gliomas that recapitulate many of the hallmarks of human glioblastoma multiforme. We used GL261 cells stably expressing luciferase to allow us to use in vivo imaging to follow tumor progression. The surgery and 3D in vivo imaging are demonstrated.

The mouse glioma 261 (GL261) is recognized as an in vivo model system that recapitulates many of the features of human glioblastoma multiforme (GBM). The ...

Dual-phase Cone-beam Computed Tomography to See, Reach, and Treat Hepatocellular Carcinoma during Drug-eluting Beads Transarterial Chemo-embolization

The advent of cone-beam computed tomography (CBCT) in the angiography suite has been revolutionary in interventional radiology. CBCT offers 3 dimensional&#160;(3D) diagnostic imaging in the interventional suite and can enhance minimally-invasive therapy beyond the limitations of 2D angiography alone. The role of CBCT has been recognized in transarterial chemo-embolization (TACE) treatment of hepatocellular carcinoma (HCC). The recent introduction of a CBCT technique: dual-phase CBCT (DP-CBCT) improves intra-arterial HCC treatment with drug-eluting beads (DEB-TACE). DP-CBCT can be used to localize liver tumors with the diagnostic accuracy of multi-phasic multidetector computed tomography (M-MDCT) and contrast enhanced magnetic resonance imaging (CE-MRI) (See the tumor), to guide intra-arterially guidewire and microcatheter to the desired location for selective therapy (Reach the tumor), and to evaluate treatment success during the procedure (Treat the tumor). The purpose of this manuscript is to illustrate how DP-CBCT is used in DEB-TACE to see, reach, and treat HCC.

Dual-phase cone-beam computed tomography (DP-CBCT) is a useful intraprocedural imaging technique for transarterial chemo-embolization treatment with drug-eluting beads of hepatocellular carcinoma. DP-CBCT has been used to perform three major steps in oncologic interventional radiology: tumor localization (see), navigation and intraprocedural catheter guidance (reach), and intraprocedural evaluation of treatment success (treat).

The advent of cone-beam computed tomography (CBCT) in the angiography suite has been revolutionary in interventional radiology. CBCT offers 3 ...

Full-root Aortic Valve Replacement by Stentless Aortic Xenografts in Patients with Small Aortic Roots

In patients with small aortic roots who need an aortic valve replacement with biological valve substitutes, the implantation of the stented pericardial valve might not meet the functional needs. The implantation of a too-small stented pericardial valve, leading to an effective orifice area indexed to a body surface area less than 0.85 cm2/m2, is regarded as prosthesis-patient mismatch (PPM). A PPM negatively affects the regression of left ventricular hypertrophy and thus the normalization of left ventricular function and the alleviation of symptoms. Persistent left ventricular hypertrophy is associated with an increased risk of arrhythmias and sudden cardiac death. In the case of predictable PPM, there are three options: 1) accept the PPM resulting from the implantation of a stented pericardial valve when comorbidities of the patient forbid the more technically demanding operative technique of implanting a larger prosthesis, 2) enlarge the aortic root to accommodate a larger stented valve substitute, or 3) implant a stentless biological valve or a homograft. Compared to classical aortic valve replacement with stented pericardial valves, the full-root implantation of stentless aortic xenografts offers the possibility of implanting a 3-4 mm larger valve in a given patient, thus allowing significant reduction in transvalvular gradients. However, a number of cardiac surgeons are reluctant to transform a classical aortic valve replacement with stented pericardial valves into the more technically challenging full-root implantation of stentless aortic xenografts. Given the potential hemodynamic advantages of stentless aortic xenografts, we have adopted full-root implantation to avoid PPM in patients with small aortic roots necessitating an aortic valve replacement. Here, we describe in detail a technique for the full-root implantation of stentless aortic xenografts, with emphasis on the management of the proximal suture line and coronary anastomoses. Limitations of this technique and alternative options are discussed.

Full-root aortic valve replacement by stentless aortic xenograft is a viable option in patients with small aortic roots. We describe, a technique for the full-root implantation of stentless aortic xenografts, with emphasis on the management of the proximal suture line and coronary anastomoses, and discuss its limitations and alternative options.

In patients with small aortic roots who need an aortic valve replacement with biological valve substitutes, the implantation of the stented pericardial ...

Standardized Technique of Aortic Valve Re-implantation for Valve-sparing Aortic Root Replacement

Despite the obvious advantages of the preservation of a normal aortic valve during aortic root replacement, the complexity of valve sparing procedures prevents a number of cardiac surgeons from incorporating them into their practice. The aim of this protocol is to describe a simplified and user-friendly technique of an aortic valve-sparing root replacement (VSRR) procedure by re-implantation of the aortic valve. Proper selection of patients and limitations of the technique are discussed.
In 54 consecutive patients, normal appearing aortic valves were re-implanted in a commercially available polyester prosthesis with pre-shaped sinuses by a simplified and standardized technique. Placement of the first row of the proximal suture line, choice of the prosthesis size, and adjustment of the height of the commissures of the patient to the fixed height of the sinus portion of the prosthesis were slightly modified from the reference techniques with the aim of increasing its feasibility for use by other cardiac surgeons. Early mortality and morbidity as well as 5-year survival, freedom from aortic valve reoperation, and freedom from recurrent moderate regurgitation were collected in all patients.
Thirty-day mortality, re-sternotomy for bleeding, re-sternotomy for mediastinitis, and the incidence of stroke were very low, 1.8% for each (1 of 54). No patient required permanent pace-maker implantation. At 5 years, survival, freedom from aortic valve reoperation, and freedom from recurrent moderate regurgitation were 97.5%, 95.2%, and 91.6%, respectively.
Mid-term results of our standardized technique of re-implantation of the aortic valve for valve-sparing aortic root replacement are very good and compare with more complex techniques reported by experienced surgeons. By following the present protocol of the standardized re-implantation technique, a greater number of cardiac surgeons can perform this procedure with comparable good results.

Valve-sparing aortic root replacement has the advantage of preserving the patient&#39;s own aortic valve. The complexity of the reported techniques to date restricts their use to a limited number of cardiac surgeons. This protocol describes step-by-step a standardized technique reproducible by a greater number of cardiac surgeons.

Despite the obvious advantages of the preservation of a normal aortic valve during aortic root replacement, the complexity of valve sparing procedures ...

Two-Dimensional X-Ray Angiography to Examine Fine Vascular Structure Using a Silicone Rubber Injection Compound

Angiography is an essential tool for the study of vascular structures in various research fields. The aim of this study is to introduce a simple angiographic method for examining the fine vascular structure of unfixed, fresh tissue using a silicone rubber injection compound and soft tissue X-ray system. This study is especially focused on flap territories used in reconstructive surgery. This study employs angiography with a silicone rubber injection compound in various experimental conditions using Sprague-Dawley rats. First, 15 mL of MV compound and 15 mL of diluent is mixed. Then, 1.5 mL of the curing agent is prepared, and a 24G catheter is cannulated in the common carotid artery of the rat. A three-way stopcock is then connected to a catheter, and the radiopaque agent, after being mixed with the prepared curing agent, is injected immediately without spillage. Finally, as the agent solidifies, the specimen is harvested, and an angiographic image is obtained using a soft tissue X-ray system. This method indicates that high-quality angiography showing fine vascular structures can be easily and simply obtained within in a short period of time.

This study presents a simple two-dimensional angiographic method to examine fine vascular structures using a silicone rubber injection compound and soft tissue X-ray system.

Angiography is an essential tool for the study of vascular structures in various research fields. The aim of this study is to introduce a simple ...

Cone Beam Intraoperative Computed Tomography-based Image Guidance for Minimally Invasive Transforaminal Interbody Fusion

Transforaminal lumbar interbody fusion (TLIF) is commonly used for the treatment of spinal stenosis, degenerative disc disease, and spondylolisthesis. Minimally invasive surgery (MIS) approaches have been applied to this technique with an associated decrease in estimated blood loss (EBL), length of hospital stay, and infection rates, while preserving outcomes with traditional open surgery. Previous MIS TLIF techniques involve significant fluoroscopy that subjects the patient, surgeon, and operating room staff to non-trivial levels of radiation exposure, particularly for complex multi-level procedures. We present a technique that utilizes an intraoperative computed tomography (CT) scan to aid in placement of pedicle screws, followed by traditional fluoroscopy for confirmation of cage placement. Patients are positioned in the standard fashion and a reference arc is placed in the posterior superior iliac spine (PSIS) followed by intraoperative CT scan. This allows for image-guidance-based placement of pedicle screws through a one-inch skin incision on each side. Unlike traditional MIS-TLIF that requires significant fluoroscopic imaging during this stage, the operation can now be performed without any additional radiation exposure to the patient or operating room staff. After completion of the facetectomy and discectomy, final TLIF cage placement is confirmed with fluoroscopy. This technique has the potential to decrease operative time and minimize total radiation exposure.

The purpose of this article is to provide image-guidance for minimally invasive transforaminal interbody fusion.

Transforaminal lumbar interbody fusion (TLIF) is commonly used for the treatment of spinal stenosis, degenerative disc disease, and spondylolisthesis. ...

A Whole Body Dosimetry Protocol for Peptide-Receptor Radionuclide Therapy (PRRT): 2D Planar Image and Hybrid 2D+3D SPECT/CT Image Methods

Peptide-receptor-radionuclide-therapy (PPRT) is a targeted therapy that combines a short-range energy radionuclide with a substrate with high specificity for cancer cell receptors. After injection, the radiotracer is distributed throughout the entire body, with a higher uptake in tissues where targeted receptors are overexpressed. The use of beta/gamma radionuclide emitters enables therapy imaging (beta-emission) and post-therapy imaging (gamma-emission) to be performed at the same time. Post-treatment sequential images permit absorbed dose calculation based on local uptake and wash-in/wash-out kinetics. We implemented a hybrid method that combines information derived from both 2D and 3D images. Serial whole-body images and blood samples are acquired to estimate the absorbed dose to different organs at risk and to lesions disseminated throughout the body. A single 3D-SPECT/CT image, limited to the abdominal region, overcomes projection overlap on planar images of different structures such as the intestines and kidneys. The hybrid 2D+3D-SPECT/CT method combines the effective half-life information derived from 2D planar images with the local uptake distribution derived from 3D images. We implemented this methodology to estimate the absorbed dose for patients undergoing PRRT with 177Lu-PSMA-617. The methodology could, however, be implemented with other beta-gamma radiotracers. To date, 10 patients have been enrolled into the dosimetry study with 177Lu-PSMA-617 combined with drug protectors for kidneys and salivary glands (mannitol and glutamate tablets, respectively). The median ratio between kidney uptake at 24 h evaluated on planar images and 3D-SPECT/CT is 0.45 (range:0.32-1.23). The comparison between hybrid and full 3D approach has been tested on one patient, resulting in a 1.6% underestimation with respect to full 3D (2D: 0.829 mGy/MBq, hybrid: 0.315 mGy/MBq, 3D: 0.320 mGy/MBq). Treatment safety has been confirmed, with a mean absorbed dose of 0.73 mGy/MBq (range:0.26-1.07) for kidneys, 0.56 mGy/MBq (0.33-2.63) for the parotid glands and 0.63 mGy/MBq (0.23-1.20) for submandibular glands, values in accordance with previously published data.

A Whole Body Dosimetry Protocol for Peptide-Receptor Radionuclide Therapy PRRT: 2D Planar Image and Hybrid 2D+3D SPECT/CT Image Methods

This method estimates the absorbed dose of different structures for peptide-receptor-radionuclide-therapy (PRRT) with the possibility of avoiding organ overlap on 2D-projections. Serial whole-body planar images permit estimation of mean absorbed doses along the whole body, while the hybrid approach, combining planar images and 3D-SPECT/CT image, overcomes the limitations of structure overlapping.

Peptide-receptor-radionuclide-therapy (PPRT) is a targeted therapy that combines a short-range energy radionuclide with a substrate with high specificity ...

Time-Resolved, Dynamic Computed Tomography Angiography for Characterization of Aortic Endoleaks and Treatment Guidance via 2D-3D Fusion-Imaging

In the United States, more than 80% of all abdominal aortic aneurysms are treated by endovascular aortic aneurysm repair (EVAR). The endovascular approach warrants good early results, but adequate follow-up imaging after EVAR is imperative to maintain long-term positive outcomes. Potential graft-related complications are graft migration, infection, fraction, and endoleaks, with the last one being the most common. The most frequently used imaging after EVAR is computed tomography angiography (CTA) and duplex ultrasound. Dynamic, time-resolved computed tomography angiography (d-CTA) is a reasonably new technique to characterize the endoleaks. Multiple scans are done sequentially around the endograft during acquisition that grants good visualization of the contrast passage and graft-related complications. This high diagnostic accuracy of d-CTA can be implemented into therapy via image fusion and reduce additional radiation and contrast material exposure.
This protocol describes the technical aspects of this modality: patient selection, preliminary image review, d-CTA scan acquisition, image processing, qualitative and quantitative endoleak characterization. The steps of integrating dynamic CTA into intra-operative fluoroscopy using 2D-3D fusion-imaging to facilitate targeted embolization are also demonstrated. In conclusion, time-resolved, dynamic CTA is an ideal modality for endoleak characterization with additional quantitative analysis. It can reduce radiation and iodinated contrast material exposure during endoleak treatment by guiding interventions.

Time-Resolved, Dynamic Computed Tomography Angiography for Characterization of Aortic Endoleaks and Treatment Guidance via 2D-3D Fusion-Imaging

Dynamic computed tomography angiography (CTA) imaging provides additional diagnostic value in characterizing aortic endoleaks. This protocol describes a qualitative and quantitative approach using time-attenuation curve analysis to characterize endoleaks. The technique of integrating dynamic CTA imaging with fluoroscopy using 2D-3D image fusion is illustrated for better image guidance during treatment.

In the United States, more than 80% of all abdominal aortic aneurysms are treated by endovascular aortic aneurysm repair (EVAR). The endovascular approach ...

Performing Intracochlear Electrocochleography During Cochlear Implantation

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation of the ear. These potentials reflect the residual function of the cochlea. In cochlear implant candidates with residual hearing, the implant electrode can directly measure ECochG responses during the implantation process. Various authors have described the ability to monitor the inner ear function by continuous ECochG measurements during the surgery. The measurement of ECochG signals during surgery is not trivial. There are no interpretable signals in up to 20% of cases. For a successful recording, a standardized procedure is recommended to achieve the highest measurement reliability and avoid possible pitfalls. Therefore, seamless collaboration between the CI surgeon and CI technician is key. This video consists of an overview of the system setup and a stepwise procedure of performing intracochlear ECochG measurements during CI surgery. It shows the surgeon's and the CI technician's roles in the process, and how a smooth collaboration between the two is made possible.

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation. In cochlear implant (CI) candidates, such inner ear potentials can be measured directly with the implant electrodes. In this video, we systematically explain how to perform ECochG recordings during CI surgery.

Electrocochleography (ECochG) measures inner ear potentials generated in response to acoustic stimulation of the ear. These potentials reflect the ...

Four-Dimensional Computed Tomography-Guided Valve Sizing for Transcatheter Pulmonary Valve Replacement

The measurements of the right ventricle (RV) and pulmonary artery (PA), for selecting the optimal prosthesis size for transcatheter pulmonary valve replacement (TPVR), vary considerably. Three-dimensional (3D) computed tomography (CT) imaging for device size prediction is insufficient to assess the displacement of the right ventricular outflow tract (RVOT) and PA, which could increase the risk of stent misplacement and paravalvular leak. The aim of this study is to provide a dynamic model to visualize and quantify the anatomy of the RVOT to PA over the entire cardiac cycle by four-dimensional (4D) cardiac CT reconstruction to obtain an accurate quantitative evaluation of the required valve size. In this pilot study, cardiac CT from sheep J was chosen to illustrate the procedures. 3D cardiac CT was imported into 3D reconstruction software to build a 4D sequence which was divided into eleven frames over the cardiac cycle to visualize the deformation of the heart. Diameter, cross-sectional area, and circumference of five imaging planes at the main PA, sinotubular junction, sinus, basal plane of the pulmonary valve (BPV), and RVOT were measured at each frame in 4D straightened models prior to valve implantation to predict the valve size. Meanwhile, dynamic changes in the RV volume were also measured to evaluate right ventricular ejection fraction (RVEF). 3D measurements at the end of the diastole were obtained for comparison with the 4D measurements. In sheep J, 4D CT measurements from the straightened model resulted in the same choice of valve size for TPVR (30 mm) as 3D measurements. The RVEF of sheep J from pre-CT was 62.1 %. In contrast with 3D CT, the straightened 4D reconstruction model not only enabled accurate prediction for valve size selection for TPVR but also provided an ideal virtual reality, thus presenting a promising method for TPVR and the innovation of TPVR devices.

This study assessed a new methodology with a straightened model generated from the four-dimensional cardiac computed tomography sequence to obtain the desired measurements for valve sizing in the application of transcatheter pulmonary valve replacement.

The measurements of the right ventricle (RV) and pulmonary artery (PA), for selecting the optimal prosthesis size for transcatheter pulmonary valve ...