The University Medical Center Utrecht Medical Ethics Committee approved the study protocol (METC 18/422), and the patient provided informed consent for the procedure and protocol.
1. Patient screening
<ol>
	<li>Patient inclusion
	<ol>
		<li>Ensure that the patient is &#62;18 years old.</li>
		<li>Ensure that the patient is symptomatic for PAD and/or ISR.</li>
	</ol>
	</li>
	<li>Patient exclusion
	<ol>
		<li>Exclude patients who cannot provide informed consent due to a language barrier or lack of comprehension.</li>
	</ol>
	</li>
</ol>
2. Vessel segmentation
<ol>
	<li>For vessel segmentation, a preoperative acquired CTA has to be uploaded into the FORS software to create a roadmap for navigation by segmenting the aorta and both iliac arteries.</li>
	<li>Select the contours of the aorta and common iliac artery in the segmentation software by moving the cursor over the arterial structures. The arteries will point out in a blue highlighted color and can be selected by clicking on them. Ensure only the arterial structures of interest are selected in this step.</li>
	<li>In this case, select the abdominal aorta and both common iliac arteries in combination with the left external iliac artery.</li>
	<li>After selection of the arteries of interest, visually inspect the segmented structures by rotating the segmented vessels.</li>
</ol>
3. Surgical preparation
<ol>
	<li>Place the patient in a supine position on the operating table, with both arms along the sides of the patient.</li>
	<li>Position the docking station at the operating table, at the left side of the patient, at the level of the upper legs.</li>
	<li>Disinfect the surgical field from the abdomen to the upper legs with chlorhexidine and expose the area of interest with sterile sheaths.</li>
</ol>
4. Ultrasound-guided puncture of the left common femoral artery
<ol>
	<li>Create an ultrasound-guided Seldinger arterial access to the common femoral artery.</li>
	<li>Introduce a 0.035 standard guidewire within the lumen of the artery.</li>
	<li>Introduce a 6 Fr sheath over the guidewire.</li>
</ol>
5. Volume registration
<ol>
	<li>To align the created roadmap according to the real-time patient position, perform volume registration. In this case, a so-called 2D-3D volume registration is performed to align the preoperative and intraoperative positions of the patient.</li>
	<li>To do this, acquire two intraoperative fluoroscopic images focusing on the field of interest, which in this case is the field of the previously implanted endograft and iliac limb. 
	NOTE: The C-arm needs to be positioned in two different orientations to acquire fluoroscopic images with an angle difference of 90&#176;. For this case, this results in one image captured with a 45&#176; left anterior oblique angle and one with a 45&#176; right anterior oblique angle. Capture and copy the images to the software.</li>
	<li>Use the visible pre-existent stent graft in both the acquired fluoroscopic images to align the segmented vessel volume with real-time fluoroscopic imaging.</li>
	<li>First, translate the segmented vessel volume onto the contours of the stent graft in the fluoroscopic images. Determine the correct windowing so the high Hounsfield values of the preoperative CTA are included to visualize the stent graft only. This can be performed by clicking on the windowing icon on the top.</li>
	<li>After translating the volume to the correct location in the fluoroscopic images, translate the center of rotation onto the center of the stent graft to enable rotation of the stent graft around its center. Rotate the stent graft in the segmented vessel volume to align the preoperative and intraoperative positions of the stent graft.</li>
	<li>To confirm alignment of the segmented vessel volume with real-time fluoroscopic imaging, adjust the windowing of the volume to orientate and compare anatomical structures, such as bony structures. Now, volume registration is successfully completed.</li>
</ol>
6. FORS shape registration
NOTE: The FORS devices are registered inside the operation theatre to enable their usage without fluoroscopy.
<ol>
	<li>Position the FORS devices in the intervention area.</li>
	<li>Acquire two fluoroscopic images with a difference in angle position of at least 30&#176; (e.g., one in the anterior posterior position and one with a 30&#176; right or left anterior oblique angle).</li>
	<li>Select the requested capturing angles in the software and rotate the C-arm toward the required position.</li>
	<li>After capturing a fluoroscopic image, copy the image by clicking on the symbol or icon presenting two documents.</li>
	<li>Analyze the projected guidewire (in yellow) and the projected catheter (in blue) over the contours on the fluoroscopic images. 
	&#8203;NOTE: The FORS technology can now be used autonomously.</li>
</ol>
7. Endovascular navigation
<ol>
	<li>Introduce the FORS guidewire through the 6 Fr sheath.</li>
	<li>Use the FORS devices to navigate through the target vessel (left iliac artery and endograft) and pass the stenotic lesion up to the abdominal aorta. Use the registered CTA segmentation as a roadmap during navigation. The black background indicates that no fluoroscopic images are captured while passing the lesion. So, the only orientation of the device position is provided by the registered segmented vessel volume.</li>
	<li>Ensure the iliac stenosis creates a resistance to the guidewire, which induces a pressure on the guidewire resulting in a dotted visualization.</li>
	<li>Do not use fluoroscopy during navigation.</li>
	<li>Exchange the FORS guidewire to a 0.014 workhorse guidewire. Because this workhorse guidewire is not supported by the FORS system; fluoroscopy must be used to obtain the wire&#39;s position.</li>
	<li>Pull out the FORS catheter.</li>
</ol>
8. Pre-PTA IVUS diameter measurements
<ol>
	<li>Using a stand-alone IVUS system, introduce the IVUS catheter over the 0.014 workhorse guidewire toward the aortic bifurcation.</li>
	<li>Visualize the intraluminal diameters from the aortic bifurcation toward the common iliac artery distal of the stenotic lesion by pulling back the IVUS catheter.</li>
	<li>Quantify the lumen diameter and cross-sectional area at the level of the lesion and the non-stenotic area of the iliac limb.</li>
	<li>Exchange the 0.014 workhorse guidewire for a 0.035 standard&#160;guidewire by using fluoroscopy.</li>
</ol>
9. Transluminal percutaneous angiography (PTA) treatment
<ol>
	<li>Use&#160;X-ray to introduce the 8 mm x 40 mm PTA balloon over the standard guidewire, and position the balloon at the stenotic lesion. Perform fluoroscopy-guided balloon inflation for 2 min.</li>
	<li>Pull back the PTA balloon.</li>
	<li>Reinflate the PTA balloon to treat the culprit lesion for a second time. The inflation process is visible by contrast enhancement of the balloon.</li>
	<li>Remove the PTA balloon and introduce the FORS catheter. Subsequently, replace the 0.035 guidewire with the 0.014 workhorse guidewire.</li>
</ol>
10. Post-PTA IVUS diameter measurements
<ol>
	<li>Using a stand-alone IVUS system, introduce the IVUS catheter over the 0.014 workhorse guidewire.</li>
	<li>Image the intraluminal diameters from the aortic bifurcation toward the common iliac artery distal of the stenotic lesion by pulling back the IVUS catheter from the aortic bifurcation toward the common iliac artery.</li>
	<li>Quantify the lumen diameter and cross-sectional area at the level of the stenotic lesion and remove the IVUS catheter.</li>
</ol>
11. Pressure measurements
<ol>
	<li>Introduce the FORS catheter over the 0.014 workhorse guidewire through the target vessel proximal to the treated stenotic lesion and pull back the standard guidewire.</li>
	<li>Position the FORS catheter proximal to the stenotic lesion and connect the back of the FORS catheter to a pressure transducer. Level and zero the pressure transducer to ensure the blood pressure measurements are accurate. Measure the blood pressure.</li>
	<li>Pull back the FORS catheter and measure the blood pressure distally to the treated stenotic lesion.</li>
	<li>Pull out the FORS catheter, standard guidewire, and sheath, and close with a percutaneous closure device.</li>
</ol>

<ol>
	<li>Song, P., 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=national+prevalence+and+risk+factors+for+peripheral+artery+disease+in+2015:+an+updated+systematic+review+and+analysis.">national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis.</a> The Lancet. Global Health. 7 (8), e1020-1030 (2019).</li><li>Aday, A. W., Matsushita, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Epidemiology+of+peripheral+artery+disease+and+polyvascular+disease.">Epidemiology of peripheral artery disease and polyvascular disease.</a> Circulation Research. 128 (12), 1818-1832 (2021).</li><li>Meijer, W. T., 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=Peripheral+arterial+disease+in+the+elderly:+The+Rotterdam+Study.">Peripheral arterial disease in the elderly: The Rotterdam Study.</a> Arteriosclerosis, Thrombosis, and Vascular Biology. 18 (2), 185-192 (1998).</li><li>Modarai, B., 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=European+Society+for+Vascular+Surgery+(ESVS)+2023+clinical+practice+guidelines+on+radiation+safety.">European Society for Vascular Surgery (ESVS) 2023 clinical practice guidelines on radiation safety.</a> European Journal of Vascular and Endovascular Surgery. 65 (2), 171-222 (2022).</li><li>Ko, 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=Health+effects+from+occupational+radiation+exposure+among+fluoroscopy-guided+interventional+medical+workers:+a+systematic+review.">Health effects from occupational radiation exposure among fluoroscopy-guided interventional medical workers: a systematic review.</a> Journal of Vascular and Interventional Radiology. 29 (3), 353-366 (2018).</li><li>Jansen, 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=Three+dimensional+visualisation+of+endovascular+guidewires+and+catheters+based+on+laser+light+instead+of+fluoroscopy+with+fiber+optic+realshape+technology:+preclinical+results.">Three dimensional visualisation of endovascular guidewires and catheters based on laser light instead of fluoroscopy with fiber optic realshape technology: preclinical results.</a> European Journal of Vascular and Endovascular Surgery. 60 (1), 135-143 (2020).</li><li>van Herwaarden, J. 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=First+in+human+clinical+feasibility+study+of+endovascular+navigation+with+Fiber+Optic+RealShape+(FORS)+technology.">First in human clinical feasibility study of endovascular navigation with Fiber Optic RealShape (FORS) technology.</a> European Journal of Vascular and Endovascular Surgery. 61 (2), 317-325 (2021).</li><li>. Optical position and/or shape sensing - Google Patents. US8773650B2 Available from: <a target="_blank" href="https://patents.google.com/patent/US8773650B2/en">https://patents.google.com/patent/US8773650B2/en</a> (2014)</li><li>Pitton, M. B., 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=Radiation+exposure+in+vascular+angiographic+procedures.">Radiation exposure in vascular angiographic procedures.</a> Journal of Vascular and Interventional Radiology. 23 (11), 1487-1495 (2012).</li><li>Sigterman, T. 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=Radiation+exposure+during+percutaneous+transluminal+angioplasty+for+symptomatic+peripheral+arterial+disease.">Radiation exposure during percutaneous transluminal angioplasty for symptomatic peripheral arterial disease.</a> Annals of Vascular Surgery. 33, 167-172 (2016).</li><li>Segal, E., 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+radiation+exposure+during+percutaneous+endovascular+revascularization+of+the+lower+extremity.">Patient radiation exposure during percutaneous endovascular revascularization of the lower extremity.</a> Journal of Vascular Surgery. 58 (6), 1556-1562 (2013).</li><li>Goni, H., 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=Radiation+doses+to+patients+from+digital+subtraction+angiography.">Radiation doses to patients from digital subtraction angiography.</a> Radiation Protection Dosimetry. 117 (1-3), 251-255 (2005).</li><li>Klaassen, J., van Herwaarden, J. A., Teraa, M., Hazenberg, C. E. V. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Superficial+femoral+artery+recanalization+using+Fiber+Optic+RealShape+technology.">Superficial femoral artery recanalization using Fiber Optic RealShape technology.</a> Medicina. 58 (7), 961 (2022).</li></ol>

Philips Medical Systems Netherlands B.V. provided a research grant according to fair market value to the Division of Surgical Specialties of the University Medical Center Utrecht to support the FORS Learn registry. The Division of Surgical specialties of the University Medical Center Utrecht has a research and consultancy agreement with Philips.

To our knowledge, this case report is the first to discuss the combination of FORS and IVUS to limit radiation exposure and exclude the use of a contrast agent during endovascular intervention for PAD. The combination of both techniques during the treatment of this specific lesion seems to be safe and feasible. Furthermore, the combination of FORS and IVUS makes it possible to limit radiation exposure (AK = 28.4 mGy; DAP = 7.87 Gy*cm2) and eliminates the use of contrast agents during the procedure. The present...

Peripheral arterial disease (PAD) is a progressive disease caused by arterial narrowing (stenosis and/or occlusions) and results in reduced blood flow toward the lower extremities. The global prevalence of PAD in the population aged 25 and over was 5.6% in 2015, indicating that about 236 million adults live with PAD worldwide1,2. As the prevalence of PAD increases with age, the number of patients will only increase in the coming years3. In recent decades, there has been a major shift from open to endovascular treatment for PAD. Treatment strategies can include plain old balloon angioplasty (POBA), potentially combined with other techniques like a drug-coated balloon, stenting, endovascular atherectomy, and classic open atherectomy (hybrid revascularization) to improve vascularization toward the target vessel.
During endovascular treatment of PAD, image guidance and navigation are conventionally provided by two-dimensional (2D) fluoroscopy and digital subtraction angiography (DSA). Some major drawbacks of fluoroscopically guided endovascular interventions include the 2D conversion of 3D structures and movements, and the grayscale display of endovascular navigation tools, which is not distinctive from the grayscale display of the surrounding anatomy during fluoroscopy. Furthermore, and more importantly, the increasing number of endovascular procedures still results in high cumulative radiation exposure, which may impact the health of vascular surgeons and radiologists. This is despite the current radiation guidelines, which are based on the &#34;as low as reasonably achievable&#34; (ALARA) principle that aims to achieve the lowest radiation exposure possible when performing a procedure safely4,5. Moreover, to assess the results of endovascular revascularization (e.g., after POBA), generally, one or two 2D digital subtraction angiograms are made with nephrotoxic contrast to estimate the dynamic improvement of blood flow. With this, eyeballing is needed to assess the increase in blood flow. Further, this technique also has limitations regarding assessments of vessel lumen diameter, plaque morphology, and the presence of flow-limiting dissection after endovascular revascularisation. To overcome these problems, new imaging technologies have been developed to improve device navigation and hemodynamics after treatment, and to reduce radiation exposure and the use of contrast material.
In the presented case, we describe the feasibility and efficacy of combining Fiber Optic RealShape (FORS) technology and intravascular ultrasound (IVUS) to reduce operator exposure during the endovascular treatment of PAD. FORS technology enables real-time, 3Dvisualization of the full shape of specially designed guidewires and catheters by using laser light, which is reflected along optical fibers instead of fluoroscopy6,7,8. Hereby, radiation exposure is reduced, and the spatial perception of endovascular navigation tools is improved by using distinctive colors while navigating during endovascular procedures. IVUS has the capacity to optimally define vessel dimensions. The aim of this article is to describe the method of combining FORS and IVUS stepwise, to show the potential of merging both techniques in view of the reduction of radiation exposure, and the improvement of navigation tasks and treatment success during endovascular procedures for the treatment of PAD.
Case presentation 
Here, we present a 65-year-old male with a history of hypertension, hypercholesterolemia, coronary artery disease, and infrarenal abdominal aortic and right common iliac artery aneurysms, treated with endovascular aneurysm repair (EVAR) in combination with a right sided iliac branched device (IBD). Years later, the patient developed acute lower extremity ischemia based on occlusion of the left iliac EVAR limb, requiring embolectomy of the left iliac EVAR limb and superficial femoral artery. In the same procedure, an aneurysm of the common iliac artery was eliminated by extension of the endograft into the external iliac artery.
Diagnosis, assessment, and plan 
During the follow-up, a routine duplex ultrasound showed an increased peak systolic velocity (PSV) within the left iliac limb of the stent graft of 245 cm/s, in comparison to a PSV of 70 cm/s proximally. This correlated with a significant stenosis of &#62;50% and a ratio of 3.5. A diagnosis of in-stent restenosis (ISR) of over 50% was subsequently confirmed by computed tomography angiography (CTA) imaging, with the additional suspicion that the stenosis was caused by thrombus. To prevent the recurrence of limb occlusion, a percutaneous transluminal angioplasty (PTA) was planned.

<table><tbody><tr><td>AltaTrack Catheter Berenstein</td><td>Philips Medical Systems Nederland B.V., Best, Netherlands</td><td>ATC55080BRN</td><td></td></tr><tr><td>AltaTrack Docking top</td><td>Philips Medical Systems Nederland B.V., Best, Netherlands</td><td></td><td></td></tr><tr><td>AltaTrack Guidewire</td><td>Philips Medical Systems Nederland B.V., Best, Netherlands</td><td>ATG35120A</td><td></td></tr><tr><td>AltaTrack Trolley</td><td>Philips Medical Systems Nederland B.V., Best, Netherlands</td><td></td><td></td></tr><tr><td>Armada 8x40mm PTA balloon</td><td>Abbott laboratories, Illinois, United States</td><td>B2080-40</td><td></td></tr><tr><td>Azurion X-ray system</td><td>Philips Medical Systems Nederland B.V, Best, Netherlands</td><td></td><td></td></tr><tr><td>Core M2 vascular system</td><td>Philips Medical Systems Nederland B.V., Best, Netherlands</td><td>400-0100.17</td><td></td></tr><tr><td>Hi-Torque Command guidewire</td><td>Abbott laboratories, Illinois, United States</td><td>2078175</td><td></td></tr><tr><td>Perclose Proglide</td><td>Abbott laboratories, Illinois, United States</td><td>12673-03</td><td></td></tr><tr><td>Rosen 0.035 stainless steel guidewire</td><td>Cook Medical, Indiana, United States</td><td>THSCF-35-180-1.5-ROSEN</td><td></td></tr><tr><td>Visions PV .014P RX catheter</td><td>Philips Medical Systems Nederland B.V., Best, Netherlands</td><td>014R</td><td></td></tr></tbody></table>

reduction of radiation exposure during endovascular treatment of peripheral arterial disease combining fiber optic realshape technology and intravascular ultrasound

Vascular surgeons and interventional radiologists face chronic exposure to low-dose radiation during endovascular procedures, which may impact their health in the long term due to their stochastic effects. The presented case shows the feasibility and efficacy of combining Fiber Optic RealShape (FORS) technology and intravascular ultrasound (IVUS) to reduce operator exposure during the endovascular treatment of obstructive peripheral arterial disease (PAD). 
FORS technology enables real-time, three-dimensional visualization of the full shape of guidewires and catheters, embedded with optical fibers that use laser light instead of fluoroscopy. Hereby, radiation exposure is reduced, and spatial perception is improved while navigating during endovascular procedures. IVUS has the capacity to optimally define vessel dimensions. Combining FORS and IVUS in a patient with iliac in-stent restenosis, as shown in this case report, enables passage of the stenosis and pre- and post-percutaneous transluminal angioplasty (PTA) plaque assessment (diameter improvement and morphology), with a minimum dose of radiation and zero contrast agent. The aim of this article is to describe the method of combining FORS and IVUS stepwise, to show the potential of merging both techniques in view of reducing radiation exposure and improving navigation tasks and treatment success during the endovascular procedure for the treatment of PAD.

The protocol used for the presented case shows the feasibility of combining the FORS technique and IVUS, with the aim to decrease radiation exposure and contrast usage in an endovascular procedure for PAD. The majority of the procedure is performed without X-ray, and zero contrast is used. Passage through the lesion is performed by using FORS (guidewire and catheter) technology. The steps in which the X-ray is used are described in the protocol; four fluoroscopic images (needed for volume and shape registration), changin...

Watch this Scientific Journal Video about Reduction of Radiation Exposure during Endovascular Treatment of Peripheral Arterial Disease Combining Fiber Optic RealShape Technology and Intravascular Ultr

Reduction of Radiation Exposure during Endovascular Treatment of Peripheral Arterial Disease Combining Fiber Optic RealShape Technology and Intravascular Ultrasound

Described here is a stepwise method of combining Fiber Optic RealShape technology and intravascular ultrasound to show the potential of merging both techniques, in view of the reduction of radiation exposure and improvement of navigation tasks and treatment success during an endovascular procedure for the treatment of peripheral arterial disease.

Vascular surgeons and interventional radiologists face chronic exposure to low-dose radiation during endovascular procedures, which may impact their ...

reduction-radiation-exposure-during-endovascular-treatment-peripheral

Research

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1.4K Views.  University Medical Center Utrecht. In de gepresenteerde casus en het gepresenteerde protocol beschreven we de haalbaarheid en werkzaamheid van het combineren van Fiber Optic RealShape, of FORS-technologie, en intravasculaire echografie, of IVUS, om de blootstelling van de operator te verminderen tijdens de endovasculaire behandeling van perifere arterieziekte of PAD. De afgelopen decennia is er een grote verschuiving geweest van open naar endovasculaire behandeling voor PAD. Tijdens endovasculaire behandeling wordt beeldgeleid...

Video: Reduction of Radiation Exposure during Endovascular Treatment of Peripheral Arterial Disease Combining Fiber Optic RealShape Technology and Intravascular Ultrasound

In vivo Near Infrared Fluorescence (NIRF) Intravascular Molecular Imaging of Inflammatory Plaque, a Multimodal Approach to Imaging of Atherosclerosis

The vascular response to injury is a well-orchestrated inflammatory response triggered by the accumulation of macrophages within the vessel wall leading to an accumulation of lipid-laden intra-luminal plaque, smooth muscle cell proliferation and progressive narrowing of the vessel lumen. The formation of such vulnerable plaques prone to rupture underlies the majority of cases of acute myocardial infarction. The complex molecular and cellular inflammatory cascade is orchestrated by the recruitment of T lymphocytes and macrophages and their paracrine effects on endothelial and smooth muscle cells.1
Molecular imaging in atherosclerosis has evolved into an important clinical and research tool that allows in vivo visualization of inflammation and other biological processes. Several recent examples demonstrate the ability to detect high-risk plaques in patients, and assess the effects of pharmacotherapeutics in atherosclerosis.4 While a number of molecular imaging approaches (in particular MRI and PET) can image biological aspects of large vessels such as the carotid arteries, scant options exist for imaging of coronary arteries.2 The advent of high-resolution optical imaging strategies, in particular near-infrared fluorescence (NIRF), coupled with activatable fluorescent probes, have enhanced sensitivity and led to the development of new intravascular strategies to improve biological imaging of human coronary atherosclerosis.
Near infrared fluorescence (NIRF) molecular imaging utilizes excitation light with a defined band width (650-900 nm) as a source of photons that, when delivered to an optical contrast agent or fluorescent probe, emits fluorescence in the NIR window that can be detected using an appropriate emission filter and a high sensitivity charge-coupled camera. As opposed to visible light, NIR light penetrates deeply into tissue, is markedly less attenuated by endogenous photon absorbers such as hemoglobin, lipid and water, and enables high target-to-background ratios due to reduced autofluorescence in the NIR window. Imaging within the NIR 'window' can substantially improve the potential for in vivo imaging.2,5
Inflammatory cysteine proteases have been well studied using activatable NIRF probes10, and play important roles in atherogenesis. Via degradation of the extracellular matrix, cysteine proteases contribute importantly to the progression and complications of atherosclerosis8. In particular, the cysteine protease, cathepsin B, is highly expressed and colocalizes with macrophages in experimental murine, rabbit, and human atheromata.3,6,7 In addition, cathepsin B activity in plaques can be sensed in vivo utilizing a previously described 1-D intravascular near-infrared fluorescence technology6, in conjunction with an injectable nanosensor agent that consists of a poly-lysine polymer backbone derivatized with multiple NIR fluorochromes (VM110/Prosense750, ex/em 750/780nm, VisEn Medical, Woburn, MA) that results in strong intramolecular quenching at baseline.10 Following targeted enzymatic cleavage by cysteine proteases such as cathepsin B (known to colocalize with plaque macrophages), the fluorochromes separate, resulting in substantial amplification of the NIRF signal. Intravascular detection of NIR fluorescence signal by the utilized novel 2D intravascular NIRF catheter now enables high-resolution, geometrically accurate in vivo detection of cathepsin B activity in inflamed plaque.
In vivo molecular imaging of atherosclerosis using catheter-based 2D NIRF imaging, as opposed to a prior 1-D spectroscopic approach,6 is a novel and promising tool that utilizes augmented protease activity in macrophage-rich plaque to detect vascular inflammation.11,12 The following research protocol describes the use of an intravascular 2-dimensional NIRF catheter to image and characterize plaque structure utilizing key aspects of plaque biology. It is a translatable platform that when integrated with existing clinical imaging technologies including angiography and intravascular ultrasound (IVUS), offers a unique and novel integrated multimodal molecular imaging technique that distinguishes inflammatory atheromata, and allows detection of intravascular NIRF signals in human-sized coronary arteries.

In vivo Near Infrared Fluorescence NIRF Intravascular Molecular Imaging of Inflammatory Plaque, a Multimodal Approach to Imaging of Atherosclerosis

We detail a new near-infrared fluorescence (NIRF) catheter for 2-dimensional intravascular molecular imaging of plaque biology in vivo. The NIRF catheter can visualize key biological processes such as inflammation by reporting on the presence of plaque-avid activatable and targeted NIR fluorochromes. The catheter utilizes clinical engineering and power requirements and is targeted for application in human coronary arteries. The following research study describes a multimodal imaging strategy that utilizes a novel in vivo intravascular NIRF catheter to image and quantify inflammatory plaque in proteolytically active inflamed rabbit atheromata.

The vascular response to injury is a well-orchestrated inflammatory response triggered by the accumulation of macrophages within the vessel wall leading ...

Osmotic Drug Delivery to Ischemic Hindlimbs and Perfusion of Vasculature with Microfil for Micro-Computed Tomography Imaging

Preclinical research in animal models of peripheral arterial disease plays a vital role in testing the efficacy of therapeutic agents designed to stimulate microcirculation. The choice of delivery method for these agents is important because the route of administration profoundly affects the bioactivity and efficacy of these agents1,2. In this article, we demonstrate how to locally administer a substance in ischemic hindlimbs by using a catheterized osmotic pump. This pump can deliver a fixed volume of aqueous solution continuously for an allotted period of time. We also present our mouse model of unilateral hindlimb ischemia induced by ligation of the common femoral artery proximal to the origin of profunda femoris and epigastrica arteries in the left hindlimb. Lastly, we describe the in vivo cannulation and ligation of the infrarenal abdominal aorta and perfusion of the hindlimb vasculature with Microfil, a silicone radiopaque casting agent. Microfil can perfuse and fill the entire vascular bed (arterial and venous), and because we have ligated the major vascular conduit for exit, the agent can be retained in the vasculature for future ex vivo imaging with the use of small specimen micro-CT3.

We show here the in vivo insertion of an osmotic pump for constant local drug delivery and the creation of hindlimb ischemia in a mouse model. Moreover, the hindlimb vasculature is perfused with Microfil, a silicone radiopaque agent, to prepare for micro-computed tomography (micro-CT) imaging.

Preclinical research in animal models of peripheral arterial disease plays a vital role in testing the efficacy of therapeutic agents designed to ...

Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery in Clinical Research

The vascular endothelium is a monolayer of cells that cover the interior of blood vessels and provide both structural and functional roles. The endothelium acts as a barrier, preventing leukocyte adhesion and aggregation, as well as controlling permeability to plasma components. Functionally, the endothelium affects vessel tone.
Endothelial dysfunction is an imbalance between the chemical species which regulate vessel tone, thombroresistance, cellular proliferation and mitosis. It is the first step in atherosclerosis and is associated with coronary artery disease, peripheral artery disease, heart failure, hypertension, and hyperlipidemia.
The first demonstration of endothelial dysfunction involved direct infusion of acetylcholine and quantitative coronary angiography. Acetylcholine binds to muscarinic receptors on the endothelial cell surface, leading to an increase of intracellular calcium and increased nitric oxide (NO) production. In subjects with an intact endothelium, vasodilation was observed while subjects with endothelial damage experienced paradoxical vasoconstriction.
There exists a non-invasive, in vivo method for measuring endothelial function in peripheral arteries using high-resolution B-mode ultrasound. The endothelial function of peripheral arteries is closely related to coronary artery function. This technique measures the percent diameter change in the brachial artery during a period of reactive hyperemia following limb ischemia.
This technique, known as endothelium-dependent, flow-mediated vasodilation (FMD) has value in clinical research settings. However, a number of physiological and technical issues can affect the accuracy of the results and appropriate guidelines for the technique have been published. Despite the guidelines, FMD remains heavily operator dependent and presents a steep learning curve. This article presents a standardized method for measuring FMD in the brachial artery on the upper arm and offers suggestions to reduce intra-operator variability.

Endothelial dysfunction is associated with numerous disease states and is predictive of adverse cardiovascular events in humans. Flow-mediated vasodilation (FMD) is a non-invasive ultrasound method of evaluating endothelial function. Methodological choices and operator experience may affect results. A systematic approach to FMD in human studies is discussed here.

The vascular endothelium is a monolayer of cells that cover the interior of blood vessels and provide both structural and functional roles. The ...

Non-fluoroscopic Catheter Tracking for Fluoroscopy Reduction in Interventional Electrophysiology

A technological platform (MediGuide) has been recently introduced for non-fluoroscopic catheter tracking. In several studies, we have demonstrated that the application of this non-fluoroscopic catheter visualization system (NFCV) reduces fluoroscopy time and dose by 90-95% in a variety of electrophysiology (EP) procedures. This can be of relevance not only to the patients, but also to the nurses and physicians working in the EP lab. Furthermore, in a subset of indications such as supraventricular tachycardias, NFCV enables a fully non-fluoroscopic procedure and allows the lab staff to work without wearing lead aprons. With this protocol, we demonstrate that even complex procedures such as ablations of atrial fibrillation, that are typically associated with fluoroscopy times of &#62;30 min in conventional settings, can safely be performed with a reduction of &#62;90% in fluoroscopy exposure by the additional use of NFCV.

Radiation exposure is an underestimated risk in complex ablation procedures. Here, we describe a protocol to significantly decrease fluoroscopy time and dosage for both the patient and the lab staff by using a novel non-fluoroscopic catheter visualization system.

A technological platform (MediGuide) has been recently introduced for non-fluoroscopic catheter tracking. In several studies, we have demonstrated that ...

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.

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 ...

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 ...

Intravascular Lithotripsy-Assisted Transfemoral Transcatheter Aortic Valve Implantation

During the last decade, transcatheter aortic valve implantation (TAVI) has evolved as a well-established therapy for aging patients suffering from symptomatic severe aortic valve stenosis. This is also reflected in the recently updated international guidelines on managing patients with valvular heart disease. A transfemoral&#160;(TF) TAVI&#160;approach has proven superior to alternative access strategies. With the introduction of intravascular lithotripsy (IVL), patients with calcified iliofemoral vascular disease and borderline intraluminal diameters have also become candidates for percutaneous TF-TAVI. Moreover, IVL reduces the risk of major vascular complications by modifying the superficial and deep vascular calcium, thereby changing the vessel compliance and controlling luminal expansion. In this way, IVL has shown to safely facilitate TF delivery of TAVI devices in patients with calcified peripheral artery disease. The present article aims to provide a detailed step-by-step description on how to perform IVL-assisted TF-TAVI safely and efficiently. Furthermore, a literature review on the outcomes obtained with this technology is included, along with a concise discussion on this unique TAVI approach.

Transcatheter aortic valve implantation (TAVI) has been shown to generate the best clinical outcomes when performed by the percutaneous transfemoral approach. Intravascular lithotripsy (IVL) can facilitate a transfemoral process in patients with calcified iliofemoral vascular disease and borderline intraluminal diameters. The present protocol describes IVL-assisted transfemoral TAVI.

During the last decade, transcatheter aortic valve implantation (TAVI) has evolved as a well-established therapy for aging patients suffering from ...

Drug Treatment by Central Venous Catheter in a Mouse Model of Angiotensin II Induced Abdominal Aortic Aneurysm and Monitoring by 3D Ultrasound

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse models, are applied to advance the understanding of the disease pathogenesis and to identify potential therapeutic targets. Testing novel drug candidates to block AAA growth in these models generally requires repeated drug administration during the time course of the experiment. Here, we describe a compiled protocol for AAA induction, insertion of an intravenous catheter to facilitate prolonged therapy, and serial AAA monitoring by 3D ultrasound. Aneurysms are induced in apolipoprotein E (ApoE) deficient mice by angiotensin II release over 28 days from osmotic mini-pumps implanted subcutaneously into the mouse back. Subsequently, the surgical procedure for external jugular vein catheterization is conducted to allow for daily intravenous drug treatment or repeated blood sampling via a subcutaneous vascular access button. Despite the two dorsal implants, the monitoring of AAA development is readily facilitated by sequential semi-automated 3D ultrasound analysis, which yields comprehensive information on the expansion of aortic diameter and volume and on aneurysm morphology, as illustrated by experimental examples.

This protocol describes the consecutive implantation of an osmotic pump to induce abdominal aortic aneurysm by angiotensin II release in apolipoprotein E (ApoE) deficient mice and of a vascular access port with a jugular vein catheter for repeated drug treatment. Monitoring of aneurysm development by 3D ultrasound is effectively conducted despite dorsal implants.

Since pharmaceutical treatment options are lacking in the clinical management of abdominal aortic aneurysm (AAA), animal models, in particular mouse ...

Occlusion of the Great and Small Saphenous Vein Using Copolymeric Glue Based on N-Butyl Cyanoacrylate and Methacryloxy Sulfolane

We present the preliminary results of a longitudinal observational study aimed at evaluating the effectiveness and safety at different short- and long-term follow-ups of vascular occlusion of the great saphenous vein (GSV) and small saphenous vein (SSV) affected by severe pathological reflux, using an innovative modified cyanoacrylate surgical glue composed of N-butyl cyanoacrylate and methacryloxy sulfolane (NBCA+MS). Ninety patients, prospectively recruited for 1 year, underwent the study with EcoColor-Doppler (ECD) to evaluate the maximum diameters of the GSV and SSV in the orthostatic position and the reflux time (RT). An RT greater than 0.5 s was considered pathologic. Clinical, etiology, anatomy, and pathophysiology (CEAP) assessment was used for the complete evaluation of each patient in the study. All the patients were treated by NBCA+MS glue to obtain vein occlusion and observed before treatment (baseline; T0), within 6 h after treatment (T1), 1 month after treatment (T2), 3 months after treatment (T3), 6 months after treatment (T4), and 1 year after treatment (T5). Chi-square (&#967;) analysis was performed to evaluate the effectiveness and safety of the treatment. All the patients participated in the entire duration of the study. Complete occlusion was maintained in 100% of patients at T1, 98.9% at T2 and T3, and 97.8% at T4 and T5 (p &lt; 0.001). None of the patients suffered from post-surgical thrombosis. No blue hyperpigmentation, or paresthesia was observed during the entire observation period. Immediately after treatment, 7.7% of patients needed painkillers; 1 week after treatment, 100% of patients returned to normal life. Vascular occlusion of the great or small saphenous vein using NBCA+MS glue is a safe procedure with persistent benefits after a 1 year follow-up. This procedure can be performed with local anesthesia, allowing a quick return to normal life. Thanks to its low invasiveness, the treatment is not painful.

Here, we present a protocol to treat the great saphenous vein (GSV) and the small saphenous vein (SSV) affected by severe pathological reflux, using an original sclerosing and embolizing cyanoacrylate-based glue composed of N-butyl cyanoacrylate and methacryloxy sulfolane (NBCA+MS).

We present the preliminary results of a longitudinal observational study aimed at evaluating the effectiveness and safety at different short- and ...

Virtual Reality-3D Modeling for Minimally Invasive Neuro-Interventional Planning

Pioneering Patient-Specific Approaches for Precision Surgery Using Imaging and Virtual Reality

Endovascular treatment of complex vascular anomalies shifts the risk of open surgical procedures to the benefit of minimally invasive endovascular procedural solutions. Complex open surgical procedures used to be the only option for the treatment of a myriad of conditions like pulmonary and aortic valve replacement as well as cerebral aneurysm repair. However, due to advancements in catheter-delivered devices and operator expertise, these procedures (along with many others) can now be performed through minimally invasive procedures delivered through a central or peripheral vein or artery. The decision to shift from an open procedure to an endovascular approach is based on multi-modal imaging, often including 3D Digital Imaging and Communications in Medicine (DICOM) imaging datasets. Utilizing these 3D images, our lab generates 3D models of the pathologic anatomy, thereby allowing the pre-procedural analysis necessary to pre-plan critical components of the catheterization lab procedure, namely, C-arm positioning, 3D measurement, and idealized road-map generation. This article describes how to take segmented 3D models of patient-specific pathology and predict generalized C-arm positions, how to measure critical two-dimensional (2D) measurements of 3D structures relevant to the 2D fluoroscopy projections, and how to generate 2D fluoroscopy roadmap analogs that can assist in proper C-arm positioning during catheterization lab procedures.

Author Spotlight: Segmentation and VR for Advanced Neurovascular Interventions

Advancements in endovascular treatment have replaced complex open surgical procedures with minimally invasive options, like valve replacement and aneurysm repair. This paper proposes using three-dimensional (3D) modeling and virtual reality to aid in C-arm positioning, angle measurements, and roadmap generation for neuro-interventional catheterization lab procedural planning, minimizing procedure time.

Reduction of Radiation Exposure during Endovascular Treatment of Peripheral Arterial Disease Combining Fiber Optic RealShape Technology and Intravascular Ultrasound

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