Name: development and evaluation of 3d-printed cardiovascular phantoms for interventional planning and training
Uploaded: 2021-01-18T14:30:00
Description: Watch this Scientific Journal Video about Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training at JoVE.com

This publication was supported by the German Heart Foundation/German Foundation of Heart Research.

Ethical approval was considered by the ethical committee of the Ludwig-Maximilians-Universit&#228;t M&#252;nchen&#160;and was waived given that the radiological datasets used in this study were retrospectively collected and fully anonymized.
Please refer to the institute&#39;s MRI safety guidelines, especially regarding the used LVAD ventricle and metal components of the flow loop.
1. Data acquisition
<ol>
	<li>Prior to creating the anatomical phantoms, select a s...

<ol>
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C., 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=Operative+Planning+in+thoracic+surgery:+A+pilot+study+comparing+imaging+techniques+and+three-dimensional+printing.">Operative Planning in thoracic surgery: A pilot study comparing imaging techniques and three-dimensional printing.</a> The Annals of Thoracic Surgery. 107 (2), 401-406 (2019).</li><li>Masaeli, R., Zandsalimi, K., Rasoulianboroujeni, M., Tayebi, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Challenges+in+three-dimensional+printing+of+bone+substitutes.">Challenges in three-dimensional printing of bone substitutes.</a> Tissue Engineering Part B: Reviews. 25 (5), 387-397 (2019).</li><li>Rafiee, M., Farahani, R. D., Therriault, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multi-material+3D+and+4D+printing:+A+survey.">Multi-material 3D and 4D printing: A survey.</a> Advanced Science. 7 (12), 1902307 (2020).</li><li>Wang, S., 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=Development+and+testing+of+an+ultrasound-compatible+cardiac+phantom+for+interventional+procedure+simulation+using+direct+three-dimensional+printing.">Development and testing of an ultrasound-compatible cardiac phantom for interventional procedure simulation using direct three-dimensional printing.</a> 3D Printing and Additive Manufacturing. 7 (6), 269-278 (2020).</li><li>D'Souza, W. D., 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=Tissue+mimicking+materials+for+a+multi-imaging+modality+prostate+phantom.">Tissue mimicking materials for a multi-imaging modality prostate phantom.</a> Medical Physics. 28 (4), 688-700 (2001).</li><li>Tejo-Otero, A., Buj-Corral, I., Fenollosa-Art&#233;s, F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=3D+printing+in+medicine+for+preoperative+surgical+planning:+A+review.">3D printing in medicine for preoperative surgical planning: A review.</a> Annals of Biomedical Engineering. 48 (2), 536-555 (2020).</li><li>Rotman, O. 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=Realistic+vascular+replicator+for+TAVR+procedures.">Realistic vascular replicator for TAVR procedures.</a> Cardiovascular Engineering and Technology. 9 (3), 339-350 (2018).</li><li>Hussein, N., 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=Hands-on+surgical+simulation+in+congenital+heart+surgery:+Literature+review+and+future+perspective.">Hands-on surgical simulation in congenital heart surgery: Literature review and future perspective.</a> Seminars in Thoracic and Cardiovascular Surgery. 32 (1), 98-105 (2020).</li><li>Fedorov, A., 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=3D+slicer+as+an+image+computing+platform+for+the+quantitative+imaging+network.">3D slicer as an image computing platform for the quantitative imaging network.</a> Magnetic resonance imaging. 30 (9), 1323-1341 (2012).</li><li>Katsura, M., Sato, J., Akahane, M., Kunimatsu, A., Abe, O. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+and+novel+techniques+for+metal+artifact+reduction+at+ct:+practical+guide+for+radiologists.">Current and novel techniques for metal artifact reduction at ct: practical guide for radiologists.</a> Radiographics. 38 (2), 450-461 (2018).</li><li>P&#233;pin, A., Daouk, J., Bailly, P., Hapdey, S., Meyer, M. 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The presented workflow allows to establish individualized models and thereby perform pre-interventional therapy planning, as well as physician training on individualized anatomies. To achieve this, patient-specific tomographic data can be used for segmentation and 3D-printing of flexible cardiovascular phantoms. By implementation of these 3D-printed models in a mock circulation, different clinical situations can be realistically simulated.
Nowadays, many therapy planning procedures focus upon ...

Individualized therapies are gaining increasing importance in modern clinical practice. Essentially, they can be classified in two groups: genetic and morphologic approaches. For individualized therapies based on unique personal DNA, either genome sequencing or the quantification of gene expression levels is necessary1. One can find these methods in oncology, for example, or in metabolic disorder treatment2. The unique morphology (i.e., anatomy) of each individual plays an important role in interventional, surgical, and prosthetic medicine. The development of individualized prostheses and pre-interventional/-operative therapy planning represent central focusses of research groups today3,4,5.
Coming from industrial prototype production, 3D-printing is ideal for this field of personalized medicine6. 3D-printing is classified as an additive manufacturing method and normally based on a layer-by-layer deposition of material. Nowadays, a broad variety of 3D-printers with different printing techniques is available, enabling processing of polymeric, biologic, or metallic materials. Due to increasing printing speeds as well as the continuous widespread availability of 3D-printers, manufacturing costs are becoming progressively less expensive. Therefore, the use of 3D-printing for pre-interventional planning in daily routines has become economically feasible7.
The aim of this study was to establish a method for generating patient-specific or disease-specific phantoms, usable in individualized therapy planning in cardiovascular medicine. These phantoms should be compatible with common imaging methods, as well as for different therapeutic approaches. A further goal was the use of the individualized anatomies as training models for physicians.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>3-matic</td>
			<td>Materialise AB</td>
			<td></td>
			<td>Software Version 15.0 - Commercial 3D-Modeling Software</td>
		</tr>
		<tr>
			<td>Affiniti 50</td>
			<td>Philips Medical Systems GmbH</td>
			<td></td>
			<td>Ultrasonic Imaging System</td>
		</tr>
		<tr>
			<td>Agilista W3200</td>
			<td>Keyence Co.</td>
			<td></td>
			<td>Polyjet 3D-Printer with a spatial resolution of 30&#181;m</td>
		</tr>
		<tr>
			<td>AR-G1L</td>
			<td>Keyence Co.</td>
			<td></td>
			<td>flexible 3D-Printing material</td>
		</tr>
		<tr>
			<td>Artis Zee</td>
			<td>Siemens Healthcare GmbH</td>
			<td></td>
			<td>Angiographic X-ray Scanner</td>
		</tr>
		<tr>
			<td>cvi42</td>
			<td>CCI Inc.</td>
			<td></td>
			<td>Software Version 5.12 - 4D Flow Analysis Software</td>
		</tr>
		<tr>
			<td>Diagnostic Catheter, Multipurpose MPA 2</td>
			<td>Cordis, A Cardinal Health company</td>
			<td></td>
			<td>Catheter for pediatric training models, Sizes 4F for infants and 5F for children, young adults</td>
		</tr>
		<tr>
			<td>Excor Ventricular Assist Device</td>
			<td>Berlin Heart GmbH</td>
			<td></td>
			<td>80 -100ml stroke volume</td>
		</tr>
		<tr>
			<td>Imeron 400 Contrast Agent</td>
			<td>Bracco Imaging</td>
			<td></td>
			<td>CT - Contrast Agent</td>
		</tr>
		<tr>
			<td>IntroGuide F</td>
			<td>Angiokard Medizintechnik GmbH</td>
			<td></td>
			<td>Guidewire with J-tip; diameter: 0.035&#34; length: 220cm</td>
		</tr>
		<tr>
			<td>Lunderquist Guidewire</td>
			<td>Cook Medical Inc.</td>
			<td></td>
			<td>(T)EVAR interventional guidewire</td>
		</tr>
		<tr>
			<td>MAGNETOM Aera</td>
			<td>Siemens Healthcare GmbH</td>
			<td></td>
			<td>MRI Scanner</td>
		</tr>
		<tr>
			<td>Magnevist Contrast Agent</td>
			<td>Bayer Vital GmbH</td>
			<td></td>
			<td>MRI - Contrast Agent</td>
		</tr>
		<tr>
			<td>Mimics</td>
			<td>Materialise AB</td>
			<td></td>
			<td>Software Version 23.0 - Commercial Segmentation Software</td>
		</tr>
		<tr>
			<td>Modeling Studio</td>
			<td>Keyence Co.</td>
			<td></td>
			<td>3D-Printer Slicing Software</td>
		</tr>
		<tr>
			<td>PVC tubing</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Radifocus Guide Wire M</td>
			<td>Terumo Europe NV</td>
			<td></td>
			<td>Straight guidewire; diameter: 0.035&#34; length: 260cm</td>
		</tr>
		<tr>
			<td>Really useful box 9L</td>
			<td>Really useful products Ltd.</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Rotigarose - Standard Agar</td>
			<td>Carl Roth GmbH</td>
			<td>3810.4</td>
			<td></td>
		</tr>
		<tr>
			<td>Solidworks</td>
			<td>Dassault Systemes SE</td>
			<td></td>
			<td>Software Version 2019-2020; CAD Design Software</td>
		</tr>
		<tr>
			<td>SOMATOM Force</td>
			<td>Siemens Healthcare GmbH</td>
			<td></td>
			<td>Computed Tomography Scanner</td>
		</tr>
		<tr>
			<td>syngo via</td>
			<td>Siemens Healthcare GmbH</td>
			<td></td>
			<td>Radiological Imaging Software</td>
		</tr>
	</tbody>
</table>

development and evaluation of 3d-printed cardiovascular phantoms for interventional planning and training

Catheter-based interventions are standard treatment options for cardiovascular pathologies. Therefore, patient-specific models could help training physicians&#39; wire-skills as well as improving planning of interventional procedures. The aim of this study was to develop a manufacturing process of patient-specific 3D-printed models for cardiovascular interventions.
To create a 3D-printed elastic phantom, different 3D-printing materials were compared to porcine biological tissues (i.e., aortic tissue) in terms of mechanical characteristics. A fitting material was selected based on comparative tensile tests and specific material thicknesses were defined. Anonymized contrast-enhanced CT-datasets were collected retrospectively. Patient-specific volumetric models were extracted from these datasets and subsequently 3D-printed. A pulsatile flow loop was constructed to simulate the intraluminal blood flow during interventions. Models&#39; suitability for clinical imaging was assessed by x-ray imaging, CT, 4D-MRI and (Doppler) ultrasonography. Contrast medium was used to enhance visibility in x-ray-based imaging. Different catheterization techniques were applied to evaluate the 3D-printed phantoms in physicians&#39; training as well as for pre-interventional therapy planning.
Printed models showed a high printing resolution (~30 &#181;m) and mechanical properties of the chosen material were comparable to physiological biomechanics. Physical and digital models showed high anatomical accuracy when compared to the underlying radiological dataset. Printed models were suitable for ultrasonic imaging as well as standard x-rays. Doppler ultrasonography and 4D-MRI displayed flow patterns and landmark characteristics (i.e., turbulence, wall shear stress) matching native data. In a catheter-based laboratory setting, patient-specific phantoms were easy to catheterize. Therapy planning and training of interventional procedures on challenging anatomies (e.g., congenital heart disease (CHD)) was possible.
Flexible patient-specific cardiovascular phantoms were 3D-printed, and the application of common clinical imaging techniques was possible. This new process is ideal as a training tool for catheter-based (electrophysiological) interventions and can be used in patient-specific therapy planning.

The described representative results focus on a few cardiovascular structures commonly used in planning, training, or testing settings. These were created using isotropic CT-datasets with a ST of 1.0 mm and a voxel size of 1.0 mm&#179;. The aortic aneurysm models&#39; wall thickness was set at 2.5 mm complying with comparative tensile testing results of the printing material (tensile strength: 0.62 &#177; 0.01 N/mm2; Fmax: 1. 55 &#177; 0.02 N; elongation: 9.01 &#177;...

Watch this Scientific Journal Video about Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training at JoVE.com

Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training

Here we present development of a mock circulation setup for multimodal therapy evaluation, pre-interventional planning, and physician-training on cardiovascular anatomies. With the application of patient-specific tomographic scans, this setup is ideal for therapeutic approaches, training, and education in individualized medicine.

Catheter-based interventions are standard treatment options for cardiovascular pathologies. Therefore, patient-specific models could help training ...

The presented method allows for the creation of patient-specific anatomical cardiovascular models for in vitro testing, teaching, and planning of procedures. This method offers a standardized approach to creating 3D printable individualized anatomical models based on radiological data sets that can be easily included in flow loops or training setups. While this modeling approach is focused on the cardiovascular system, it can be transferred to other anatomical structures.The quality of the radiological data set has a big influence on the difficulties encountered during modeling. For the first models, use a dataset with minimal movement artifacts and a high spatial resolution. To begin, define a range of Hounsfield unit values by opening the thresholding tool resulting in a combined mask of the contrast enhanced blood volume and bone structures.Remove all bone parts that are undesirable in the final 3D model by using the Split Mask tool, which enables the marking and separation of multiple areas in overall slices based on Hounsfield values and location. Following this separation, ensure that a mask containing the contrast enhanced blood volume remains. This can be done by scrolling through the coronal and axial planes and matching the created mask with the underlying dataset.From this mask, calculate a rendered 3D polygon surface model. Click the Local Smoothing tool to adjust the surface of the segmented model manually and locally. Focus on removing rough polygon shapes, single peaks, and rough edges created by previous trimming operations.To allow the later connection of the model to a flow loop, include tubular parts with defined diameters adjusted to the available hose connectors and tube diameters. To place a datum plane parallel to the opening cross-section of the vessels, select the tool, Create Datum Plane, and use the preset 3 Point Plane. Next, click on three equally spaced points on the vessel's cross-section to create the plane.Input an offset of 10 millimeters in the command window and confirm the operation. Select the draw sketch tool from the menu and choose the previously created datum plane as the location of the sketch. In the sketch, place a circle roughly on the center line of the vessel and set the radius constraint to match the outer diameter of the hose connector.From the created sketch, use the Extrude tool to create a cylinder with a length of 10 millimeters. Orient the extrusion to move away from the vessel opening to create a distance between the cylinder and the vessel cross section of 10 millimeters. Then use the Loft tool to create a connection between the vessel ending and the geometrically defined cylinder.Ensure a smooth transition between the two cross sections, thereby avoiding turbulence and low flow areas in the final 3D flow model. Finally, use the Hollow tool to make a hollow blood space in the command window, and put the required wall thickness and set the direction of the hollowing process to move outward. Confirm the selection to execute the hollowing process.After uploading the printing file from the slicing software to the 3D printer, ensure that the amount of printing material and support material in the printer's cartridges is sufficient for the 3D model and start the print. Following the printing process, remove the support material from the finished model. First, remove the support material manually by gently squeezing the model.Place the model on the sink, and then immerse it in water or a respective solvent after removing the cover. Dry the model in an incubator set to 40 degrees Celsius overnight. On the next day, embed the model in 1%agar.Use a plastic box with at least two centimeter side margins around the model and drill holes into the walls to allow the tubes to be connected from the vessels to the pump and the reservoir. Add agar to water and bring it to a boil. After stirring the mixture, let it cool for five minutes and pour it into the box to create a bed of at least two centimeter height.While the agar bed sets, connect the model to a non-compliant PVC tube using commercial hose connectors at every opening. Use zip ties to fix the connection between the hose connectors and the 3D model and ensure that there is no fluid leakage. Guide the PVC tubes through the drilled holes into the box, then place the model on top of the set agar bed.To prevent agar leaking from these holes, use heatproof modeling clay to seal it. Next, fill the box with agar and cover the model by adding a two centimeter layer on top. Allow the agar to fully cool and set for an hour at room temperature.Agitate the ventricle using a piston pump with a stroke volume of 120 to 150 milliliters. For CT imaging, place the entire flow loop within the CT scanner with the drive unit standing close by. Connect the contrast agent pump directly to the reservoir of the flow loop so the flooding of the model with contrast agent can be simulated during scanning.This is especially useful for visualizing vascular pathologies. Perform CT as a dynamic scan over the whole model to visualize contrast agent inflow. Inject 100 milliliters of one to 10 diluted iodinated contrast agent into the model's reservoir at a speed of four milliliters per second.Start the scan using bolus triggering in the leading tube with a 100 Hounsfield unit threshold in a four second delay. To perform sonography, put a small amount of ultrasonic gel on top of the agar block to reduce artifacts. Start the pump and use the ultrasonic head to locate the anatomical structure of interest.Use 2D echo mode to evaluate leaflet movement as well as the opening and closing behavior of the valve. Use color Doppler to evaluate blood flow across the valve and spectral Doppler to quantify the flow velocity following the heart valve. Insert an access port into the PVC tube directly below the 3D model to allow for an easier access of the anatomy with a cardiac catheter or guide wire.After starting the flow loop, check for leakage at the port entrance point. If necessary, use a two component adhesive to seal the opening. Place the 3D model on the patient table underneath the C arms of the x-ray machine.Use x-ray imaging to guide the catheter and guide wires through the anatomic structure. For 4D MRI, use a 1.5 Tesla scanner and ensure that the acquisition protocol consists of a non-contrast enhanced MRA in the 4D flow sequence. Acquire an isotropic dataset with 25 phases in a slice thickness of 1.2 millimeters.Set the velocity encoding at 100 centimeters per second. Perform the 4D flow image analysis with a commercially available software. First, import the 4D MRI dataset by selecting it from the flash drive, then perform semi-automated offset correction and correction of aliasing to improve image quality.The center line of the vessel will be automatically traced, and the software extracts the 3D volume. Finally, perform quantitative analysis of flow parameters by clicking on the individual tabs in the analysis window. Flow visualization, path line visualization, and flow vector can be visualized without further input.For quantification of pressure and wall shear stress in the representative tab, place two planes by clicking on the Add Plane button. Move the planes to the ROI by dragging them along the center line so that one plane is placed at the beginning of the ROI and one at the end. The pressure drop across the ROI and wall shear stress will be visualized and quantified in the diagram next to the 3D model.The presented 3D printed models offer a wide range of possibilities in CT imaging. The printed material can be easily distinguished from the surrounding agar and possible metallic implants. Therefore, the use of a contrast agent is normally not required, except for generating dynamic imaging sequences.When using ultrasonic imaging, it is possible to distinguish between the model's wall, the surrounding agar, and thin dynamic objects like heart valve leaflets. The agar layer on top of the model provides realistic haptic feedback during the scanning process. Flow analysis within the flow loop offers a wide range of possible applications and pre-interventional imaging.4D MRI sequence enables visualization of fluid flow, turbulences, and wall shear stress within the 3D printed model, making it possible to analyze flow patterns following artificial heart valves. This workflow can be transferred to different interventional medical procedures for training or planning purposes. The technique allows for a closer in vitro examination of the flow behavior in large cardiovascular vessels and offers great potential for individualized therapy planning.

development-evaluation-3d-printed-cardiovascular-phantoms-for

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Medicine

Renal Capsule Xenografting and Subcutaneous Pellet Implantation for the Evaluation of Prostate Carcinogenesis and Benign Prostatic Hyperplasia

New therapies for two common prostate diseases, prostate cancer (PrCa) and benign prostatic hyperplasia (BPH), depend critically on experiments evaluating their hormonal regulation. Sex steroid hormones (notably androgens and estrogens) are important in PrCa and BPH; we probe their respective roles in inducing prostate growth and carcinogenesis in mice with experiments using compressed hormone pellets. Hormone and/or drug pellets are easily manufactured with a pellet press, and surgically implanted into the subcutaneous tissue of the male mouse host. We also describe a protocol for the evaluation of hormonal carcinogenesis by combining subcutaneous hormone pellet implantation with xenografting of prostate cell recombinants under the renal capsule of immunocompromised mice. Moreover, subcutaneous hormone pellet implantation, in combination with renal capsule xenografting of BPH tissue, is useful to better understand hormonal regulation of benign prostate growth, and to test new therapies targeting sex steroid hormone pathways.

We describe the manufacture of compressed hormone pellets, as well as subcutaneous surgical implantation into mice. This strategy can be combined with the growth of cell and tissue xenografts under the renal capsule of athymic nude mice to evaluate hormonal carcinogenesis and regulation of benign prostate growth.

New therapies for two common prostate diseases,  prostate cancer (PrCa) and benign prostatic hyperplasia (BPH), depend  critically on experiments ...

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 ...

Inducing Myointimal Hyperplasia Versus Atherosclerosis in Mice: An Introduction of Two Valid Models

Various in vivo laboratory rodent models for the induction of artery stenosis have been established to mimic diseases that include arterial plaque formation and stenosis, as observed for example in ischemic heart disease. Two highly reproducible mouse models&#160;&#8211;&#160;both resulting in artery stenosis but each underlying a different pathway of development&#160;&#8211; are introduced here. The models represent the two most common causes of artery stenosis; namely one mouse model for each myointimal hyperplasia, and atherosclerosis are shown. To induce myointimal hyperplasia, a balloon catheter injury of the abdominal aorta is performed. For the development of atherosclerotic plaque, the ApoE -/- mouse model in combination with western fatty diet is used. Different model-adapted options for the measurement and evaluation of the results are named and described in this manuscript. The introduction and comparison of these two models provides information for scientists to choose the appropriate artery stenosis model in accordance to the scientific question asked.

This video shows two models of intimal plaque development in murine arteries and emphasizes the differences in myointimal hyperplasia and atherosclerosis.

Various in vivo laboratory rodent models for the induction of artery stenosis have been established to mimic diseases that include arterial plaque ...

A Multicenter MRI Protocol for the Evaluation and Quantification of Deep Vein Thrombosis

We evaluated a magnetic resonance venography (MRV) approach with gadofosveset to quantify total thrombus volume changes as the principal criterion for treatment efficacy&#160;in a multicenter randomized study comparing edoxaban monotherapy with a heparin/warfarin regimen for acute, symptomatic lower extremities deep vein thrombosis (DVT) treatment. We also used a direct thrombus imaging approach (DTHI, without the use of a contrast agent) to quantify fresh thrombus. We then sought to evaluate the reproducibility of the analysis methodology and applicability of using 3D magnetic resonance venography and direct thrombus imaging for the quantification of DVT in a multicenter trial setting. From 10 randomly selected subjects participating in the edoxaban Thrombus Reduction Imaging Study (eTRIS), total thrombus volume in the entire lower extremity deep venous system was quantified bilaterally. Subjects were imaged using 3D-T1W gradient echo sequences before (direct thrombus imaging, DTHI) and 5 min after injection of 0.03 mmol/kg of gadofosveset trisodium (magnetic resonance venography, MRV). The margins of the DVT on corresponding axial, curved multi-planar reformatted images were manually delineated by two observers to obtain volumetric measurements of the venous thrombi. MRV was used to compute total DVT volume, whereas DTHI was used to compute volume of fresh thrombus. Intra-class correlation (ICC) and Bland Altman analysis were performed to compare inter and intra-observer variability of the analysis. The ICC for inter and intra-observer variability was excellent (0.99 and 0.98, p &#60;0.001, respectively) with no bias on Bland-Altman analysis for MRV images. For DTHI images, the results were slightly lower (ICC = 0.88 and 0.95 respectively, p &#60;0.001), with bias for inter-observer results on Bland-Altman plots. This study showed feasibility of thrombus volume estimation in DVT using MRV with gadofosveset trisodium, with good intra- and inter-observer reproducibility in a multicenter setting.

The goal of this study is to use magnetic resonance venography with long-circulating gadolinium-based contrast agent and direct thrombus imaging for quantitative evaluation of DVT volume in a multicenter, clinical trial setting. Inter- and intra-observer variability assessments were conducted, and reproducibility of the protocol was determined.

We evaluated a magnetic resonance venography (MRV) approach with gadofosveset to quantify total thrombus volume changes as the principal criterion for ...

Lung Fixation under Constant Pressure for Evaluation of Emphysema in Mice

Emphysema is a significant feature of chronic obstructive pulmonary disease (COPD). Studies involving an emphysematous mouse model require optimal lung fixation to produce reliable histological specimens of the lung. Due to the nature of the lung&rsquo;s structural composition, which consists largely of air and tissue, there is a risk that it collapses or deflates during the fixation process. Various lung fixation methods exist, each of which has its own advantages and disadvantages. The lung fixation method presented here utilizes constant pressure to enable optimal tissue evaluation for studies using an emphysematous mouse lung model. The main advantage is that it can fix many lungs with the same condition at one time. Lung specimens are obtained from chronic cigarette smoke-exposed mice. Lung fixation is performed using specialized equipment that enables the production of constant pressure. This constant pressure maintains the lung in a reasonably inflated state. Thus, this method generates a histological specimen of the lung that is suitable to evaluate cigarette smoke-induced mild emphysema.

Presented here is a useful protocol for lung fixation that creates a stable condition for histological evaluate of lung specimens from a mouse model of emphysema. The main advantage of this model is that it can fix many lungs with the same constant pressure without lung collapse or deflation.

Emphysema is a significant feature of chronic obstructive pulmonary disease (COPD). Studies involving an emphysematous mouse model require optimal lung ...

Transaxillary First Rib Resection for Treatment of the Thoracic Outlet Syndrome

Thoracic outlet syndrome (TOS) is a common disorder that causes a significant loss of productivity. The transaxillary first rib resection (TFRR) protocol has been used for the decompression of trapped neurovascular structures in the TOS. Among the other surgical procedures, the advantage of the TFRR is that it has the smallest rate of recurrence and better cosmetic outcomes. The disadvantage of TFRR is that it provides a narrow, and deep working corridor that makes obtaining vascular control challenging.

Here, we present a protocol of the transaxillary resection of the first rib for treatment of thoracic outlet syndrome caused by compression of the brachial plexus, subclavian vein and artery.

Thoracic outlet syndrome (TOS) is a common disorder that causes a significant loss of productivity. The transaxillary first rib resection (TFRR) protocol ...

Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. However, the evaluation of right ventricular pressure (RVP) and pulmonary artery pressure (PAP) remains technically challenging in mice. RVP and PAP are more difficult to measure than left ventricular pressure because of the anatomical differences between the left and right heart systems. In this paper, we describe a stable right heart hemodynamic measurement method and its validation using healthy and PAH mice. This method is based on open-chest surgery and mechanical ventilation support. It is a complicated procedure compared to closed chest procedures. While a well-trained surgeon is required for this surgery, the advantage of this procedure is that it can generate both RVP and PAP parameters at the same time, so it is a preferable procedure for the evaluation of PAH models.

Here, we present a protocol to perform an invasive hemodynamic assessment of the right ventricle and pulmonary artery in mice using an open-chest surgery approach.

Pulmonary arterial hypertension (PAH) is a chronic and severe cardiopulmonary disorder. Mice are a popular animal model used to mimic this disease. ...

Novel Percutaneous Approach for Deployment of 3D Printed Coronary Stenosis Implants in Swine Models of Ischemic Heart Disease

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally (3D) printed coronary implants can be employed to percutaneously create a focal coronary stenosis. However, reliable delivery of the implants can be difficult without the use of ancillary equipment. We describe the use of a mother-and-child coronary guide catheter for stabilization of the implant and for effective delivery of the 3D printed implant to any desired location along the length of the coronary vessel. The focal coronary narrowing was confirmed under coronary cineangiography and the functional significance of the coronary stenosis was assessed using gadolinium-enhanced first-pass cardiac perfusion MRI. We showed that reliable delivery of 3D printed coronary implants in swine models (n = 11) of ischemic heart disease can be achieved through repurposing mother-and-child coronary guide catheters. Our technique simplifies the percutaneous delivery of coronary implants to create closed-chest swine models of focal coronary artery stenosis and can be performed expeditiously, with a low procedural failure rate.

We describe a novel, cost-effective, and efficient technique for percutaneous delivery of three-dimensionally printed coronary implants to create closed-chest swine models of ischemic heart disease. The implants were fixed in place using a mother-and-child extension catheter with high success rate.

Minimally invasive methods for creating models of focal coronary narrowing in large animals are challenging. Rapid prototyping using three-dimensionally ...

Interventional Diagnostic Procedure: A Practical Guide for the Assessment of Coronary Vascular Function

Approximately 40% of patients undergoing invasive coronary angiography for investigation of angina are found to have no obstructive coronary artery disease (ANOCA). Abnormal coronary function underlies coronary vasomotion syndromes including coronary endothelial dysfunction, microvascular angina, vasospastic angina, post-PCI angina and myocardial infarction with no obstructive coronary arteries (MINOCA). Each of these endotypes are distinct subgroups, characterized by specific disease mechanisms. Diagnostic criteria and linked therapy for these conditions are now established by expert consensus and clinical guidelines.
Coronary function tests are performed as an adjunctive interventional diagnostic procedure (IDP) in appropriately selected patients during coronary angiography. This aids differentiation of patients according to endotype. The IDP includes two distinct components: a diagnostic guidewire test and a pharmacological coronary reactivity test. The tests last approximately 5 minutes for the former and 10-15 minutes for the latter. Patient safety and staff education are key.
The diagnostic guidewire test measures parameters of coronary flow limitation (fractional flow reserve [FFR], coronary flow reserve [CFR], microvascular resistance [index of microvascular resistance (IMR)], basal resistance index, and vasodilator function [CFR, resistive reserve ratio (RRR)]).
The pharmacological coronary reactivity test measures the vasodilator potential and propensity to vasospasm of both the main coronary arteries and the micro-vessels. It involves intra-coronary infusion of acetylcholine and glyceryl trinitrate (GTN). Acetylcholine is not licensed for parenteral use and is therefore prescribed on a named-patient basis. Vasodilatation is the normal, expected response to infusion of physiological concentrations of acetylcholine. Vascular spasm represents an abnormal response, which supports the diagnosis of vasospastic angina.
The purpose of this practical guide is to provide information on the preparation and administration of the IDP in clinical practice. It discusses some key preparation and safety considerations, as well as tips for procedural success. The IDP supports stratified medicine for a personalized approach to health and wellbeing.

The purpose of this practical guide is to provide information on the preparation and administration of an interventional diagnostic procedure in clinical practice. It discusses some key preparation and safety considerations, as well as tips for procedural success.

Approximately 40% of patients undergoing invasive coronary angiography for investigation of angina are found to have no obstructive coronary artery ...

A Personalized 3D-Printed Model for Preoperative Evaluation in Thyroid Surgery

The anatomic structure of the surgical area of thyroid cancer is complex. It is very important to comprehensively and carefully evaluate the tumor location and its relation with the capsule, trachea, esophagus, nerves, and blood vessels before operation. This paper introduces an innovative 3D-printed model establishment method based on computerized tomography (CT) DICOM images. We established a personalized 3D-printed model of the cervical thyroid surgery field for each patient who needed thyroid surgery to help clinicians evaluate the key points and difficulties of the surgery and select the operation methods of key parts as a basis. The results showed that this model is conducive to preoperative discussion and the formulation of operation strategies. In particular, as a result of the clear display of the recurrent laryngeal nerve and parathyroid gland locations in the thyroid operation field, injury to them can be avoided during surgery, the difficulty of thyroid surgery reduced, and the incidence of postoperative hypoparathyroidism and complications related to recurrent laryngeal nerve injury reduced too. Moreover, this 3D-printed model is intuitive and aids communication for the signing of informed consent by patients before surgery.

Here, a new method of establishing a personalized 3D-printed model for preoperative evaluation of thyroid surgery is proposed. It is conducive to preoperative discussion, reducing the difficulty of thyroid surgery.