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概要

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.

Abstract

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.

Introduction

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 worldwide^1,2. 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 "as low as reasonably achievable" (ALARA) principle that aims to achieve the lowest radiation exposure possible when performing a procedure safely^4,5. 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 fluoroscopy^6,7,8. 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 >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.

Protocol

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

1. Patient inclusion
   1. Ensure that the patient is >18 years old.
   2. Ensure that the patient is symptomatic for PAD and/or ISR.
2. Patient exclusion
   1. Exclude patients who cannot provide informed consent due to a language barrier or lack of comprehension.

2. Vessel segmentation

1. 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.
2. 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.
3. In this case, select the abdominal aorta and both common iliac arteries in combination with the left external iliac artery.
4. After selection of the arteries of interest, visually inspect the segmented structures by rotating the segmented vessels.

3. Surgical preparation

1. Place the patient in a supine position on the operating table, with both arms along the sides of the patient.
2. Position the docking station at the operating table, at the left side of the patient, at the level of the upper legs.
3. Disinfect the surgical field from the abdomen to the upper legs with chlorhexidine and expose the area of interest with sterile sheaths.

4. Ultrasound-guided puncture of the left common femoral artery

1. Create an ultrasound-guided Seldinger arterial access to the common femoral artery.
2. Introduce a 0.035 standard guidewire within the lumen of the artery.
3. Introduce a 6 Fr sheath over the guidewire.

5. Volume registration

1. 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.
2. 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°. For this case, this results in one image captured with a 45° left anterior oblique angle and one with a 45° right anterior oblique angle. Capture and copy the images to the software.
3. Use the visible pre-existent stent graft in both the acquired fluoroscopic images to align the segmented vessel volume with real-time fluoroscopic imaging.
4. 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.
5. 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.
6. 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.

6. FORS shape registration

NOTE: The FORS devices are registered inside the operation theatre to enable their usage without fluoroscopy.

1. Position the FORS devices in the intervention area.
2. Acquire two fluoroscopic images with a difference in angle position of at least 30° (e.g., one in the anterior posterior position and one with a 30° right or left anterior oblique angle).
3. Select the requested capturing angles in the software and rotate the C-arm toward the required position.
4. After capturing a fluoroscopic image, copy the image by clicking on the symbol or icon presenting two documents.
5. Analyze the projected guidewire (in yellow) and the projected catheter (in blue) over the contours on the fluoroscopic images.
   ​NOTE: The FORS technology can now be used autonomously.

7. Endovascular navigation

1. Introduce the FORS guidewire through the 6 Fr sheath.
2. 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.
3. Ensure the iliac stenosis creates a resistance to the guidewire, which induces a pressure on the guidewire resulting in a dotted visualization.
4. Do not use fluoroscopy during navigation.
5. 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's position.
6. Pull out the FORS catheter.

8. Pre-PTA IVUS diameter measurements

1. Using a stand-alone IVUS system, introduce the IVUS catheter over the 0.014 workhorse guidewire toward the aortic bifurcation.
2. Visualize the intraluminal diameters from the aortic bifurcation toward the common iliac artery distal of the stenotic lesion by pulling back the IVUS catheter.
3. Quantify the lumen diameter and cross-sectional area at the level of the lesion and the non-stenotic area of the iliac limb.
4. Exchange the 0.014 workhorse guidewire for a 0.035 standard guidewire by using fluoroscopy.

9. Transluminal percutaneous angiography (PTA) treatment

1. Use 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.
2. Pull back the PTA balloon.
3. Reinflate the PTA balloon to treat the culprit lesion for a second time. The inflation process is visible by contrast enhancement of the balloon.
4. Remove the PTA balloon and introduce the FORS catheter. Subsequently, replace the 0.035 guidewire with the 0.014 workhorse guidewire.

10. Post-PTA IVUS diameter measurements

1. Using a stand-alone IVUS system, introduce the IVUS catheter over the 0.014 workhorse guidewire.
2. 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.
3. Quantify the lumen diameter and cross-sectional area at the level of the stenotic lesion and remove the IVUS catheter.

11. Pressure measurements

1. 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.
2. 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.
3. Pull back the FORS catheter and measure the blood pressure distally to the treated stenotic lesion.
4. Pull out the FORS catheter, standard guidewire, and sheath, and close with a percutaneous closure device.

Representative Results

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), changing of guidewires (0.035 standard and 0.014 workhorse), and during inflation of the PTA balloon (Table 1).

Instead of making a (contrast) 2D digital subtraction angiogram, the effect of POBA in this case is quantified by using IVUS. The lumen diameter increased from 4.8 mm pre-POBA to 7.0 mm post-POBA, and the cross-sectional lumen area increased from 27.7 mm² to 43.8 mm², respectively (Figure 1). After POBA, blood pressure measurements showed no significant drop distal to the area under consideration compared with the aortic area (blood pressure of 103/73 and 106/73 mmHg, respectively), confirming an adequate treatment.

The total fluoroscopic time was 1 min 53 s, with a total air kerma (AK) of 28.4 mGy and a dosis area product (DAP) of 7.87 Gy/cm². Follow-up duplex ultrasound examination showed no residual stenotic lesion, and the patient indicated that walking distance improved. An overview of all IVUS measurements, blood pressure measurements, and total radiation exposure is presented in Table 2.

The combination of FORS and IVUS shows to be feasible in reducing radiation exposure and contrast usage, and enables an accurate treatment of a stenotic lesion and quantification of the result.

	Presented protocol	Conventional therapy
Vessel volume segmentation	No radiation	Not applicable
Volume registration	2x Single shot exposures	Not applicable
FORS shape registration	2x Single shot exposures	Not Applicable
Endovascular navigation	No radiation (FORS)	Fluoroscopy
Changing guidewires	Fluoroscopy	Fluoroscopy
Quantification of stenotic lesion	No radiation, no contrast (IVUS)	2x DSA with contrast
PTA treatment	Fluoroscopy	Fluoroscopy
Quantification of treatment success	No radiation, no contrast (IVUS)	2x DSA with contrast
Pressure measurements	No radiation (FORS)	Fluoroscopy

Table 1: Overview of the presented protocol and the use of radiation exposure, FORS, and IVUS during the procedure compared to conventional PTA treatment of a stenotic lesion. PTA = percutaneous transluminal angioplasty; FORS = Fiber Optic Realshape; IVUS = intravascular ultrasound; DSA = digital subtraction angiography.

IVUS Lumen diameter
	Pre-treatment	4.0 mm
	Post-treatment	7.0 mm
IVUS Cross-sectional lumen area
	Pre-treatment	27.7 mm2
	Post-treatment	43.8 mm2
Post-treatment pressure measurement
	Cranial to culprit area	103/73 mmHg
	Distal to culprit area	106/73 mmHg
Radiation exposure parameters
	Fluoroscopy time	00:01:53 (HH:MM:SS)
	Air Kerma (AK)	28.4 mGy
	Dosis Area Product (DAP)	7.87 Gy*cm2

Table 2: Overview of pre- and posttreatment IVUS-measured lumen diameter and cross-sectional lumen area, posttreatment pressure measurements, and radiation exposure outcomes. IVUS = intravascular ultrasound.

Figure 1: Pre and post treatment images. (A) Pretreatment assessment of the stenotic lesion and (B) post-treatment quantification of treatment success using IVUS. The minimal lumen diameter increases from 4.8 mm to 7.0 mm, and the cross-sectional lumen area from 27.7 mm² to 43.8 mm² after PTA treatment. Please click here to view a larger version of this figure.

Discussion

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 presented amount of radiation exposure and contrast volume are much lower compared to those from procedures in the same anatomical region reported in the literature; however, direct comparison of these results is difficult^9,10,11. Radiation exposure and related parameters in peripheral endovascular interventions are significantly influenced by patient-related parameters (e.g., body mass index) and lesion characteristics (length, severity, and morphology). In general, however, the culprit lesion must be visualized for navigation purposes and to quantify the effect the endovascular treatment (in this case, POBA), which represents a relatively large proportion of the total procedural radiation exposure¹². Since FORS is used in combination with a roadmap during navigation and IVUS for the assessment of treatment outcome, it is not necessary to obtain digital subtraction angiograms in this case. It is therefore very likely that significantly less radiation is used in this case than what would have been used in a conventional approach with fluoroscopic and DSA imaging.

A limitation of the presented case is that it concerns a relatively low complex lesion (short and non-calcified/TASC A), making this procedure a relatively straightforward intervention. However, Klaassen et al.¹³ showed that the use of a FORS guidewire and catheter is feasible for the recanalization of long and complex superficial femoral artery lesions (TASC D). The added value of combining FORS and IVUS has not been described yet.

Furthermore, the 2D volume registration of the roadmap is simplified in this case because of the pre-existing EVAR endograft. The aortic bifurcation and both iliac arteries are fairly fixed in terms of the anatomic position, so the differences between the segmented CTA and the actual anatomical position on the operating room (OR) table are relatively small. Arteries in the upper and especially lower leg, conversely, have much more freedom of movement. This increases the possibility of differences in anatomical orientation and rotation between the preoperative CTA and the actual position on the operating table, making it more challenging to precisely position the created roadmap via 2D volume registration. In these cases, positioning of the roadmap has to be adapted to the actual situation during the procedure.

Finally, volume and shape registration require additional and complicated tasks, and the current version of the FORS-enabled guidewire and catheter needs further development. The FORS guidewire is not back-loadable due to its tethered connection to the system. This makes it impossible to change a catheter over the wire once the guidewire is placed in the body, and many additional steps are currently required to switch from FORS to IVUS and vice versa. Addressing these issues in future versions of this guidewire will make it easier to use these technologies simultaneously.

In this case, we describe a successful treatment of a stenotic lesion in the proximal part of an iliac limb of an EVAR endograft, in which the combination of image fusion, FORS, and IVUS technology leads to minimal radiation exposure and no contrast medium use. In an era of increasing numbers of endovascular procedures and correlated increasing cumulative radiation exposure for both patients and treatment teams, the combination of these technologies shows a safe turn toward the possibility of minimizing or even eliminating radiation exposure and contrast usage during these procedures. In addition, the use of IVUS to quantify stenotic lesions and the direct treatment effect perioperatively provides a more objective outcome measure compared to the surgeons assessment of contrast flow during DSA. Future developments should aim at merging both techniques in one catheter, using the same interface and software as one solution. Furthermore, future research must include more patients with more complex lesions to demonstrate the effect on radiation exposure and contrast use, and to show whether merging of both techniques in one device has potential.

Materials

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