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 border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<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

JoVE Journal

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1.3K Views.  University Medical Center Utrecht. 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. 

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

X-ray Dose Reduction through Adaptive Exposure in Fluoroscopic Imaging

X-ray fluoroscopy is widely used for image guidance during cardiac intervention. However, radiation dose in these procedures can be high, and this is a significant concern, particularly in pediatric applications. Pediatrics procedures are in general much more complex than those performed on adults and thus are on average four to eight times longer1. Furthermore, children can undergo up to 10 fluoroscopic procedures by the age of 10, and have been shown to have a three-fold higher risk of developing fatal cancer throughout their life than the general population2,3.
We have shown that radiation dose can be significantly reduced in adult cardiac procedures by using our scanning beam digital x-ray (SBDX) system4-- a fluoroscopic imaging system that employs an inverse imaging geometry5,6 (Figure 1, Movie 1 and Figure 2). Instead of a single focal spot and an extended detector as used in conventional systems, our approach utilizes an extended X-ray source with multiple focal spots focused on a small detector. Our X-ray source consists of a scanning electron beam sequentially illuminating up to 9,000 focal spot positions. Each focal spot projects a small portion of the imaging volume onto the detector. In contrast to a conventional system where the final image is directly projected onto the detector, the SBDX uses a dedicated algorithm to reconstruct the final image from the 9,000 detector images.
For pediatric applications, dose savings with the SBDX system are expected to be smaller than in adult procedures. However, the SBDX system allows for additional dose savings by implementing an electronic adaptive exposure technique. Key to this method is the multi-beam scanning technique of the SBDX system: rather than exposing every part of the image with the same radiation dose, we can dynamically vary the exposure depending on the opacity of the region exposed. Therefore, we can significantly reduce exposure in radiolucent areas and maintain exposure in more opaque regions. In our current implementation, the adaptive exposure requires user interaction (Figure 3). However, in the future, the adaptive exposure will be real time and fully automatic.
We have performed experiments with an anthropomorphic phantom and compared measured radiation dose with and without adaptive exposure using a dose area product (DAP) meter. In the experiment presented here, we find a dose reduction of 30%.

We are developing a dynamic adaptive exposure technique using our scanning beam digital X-ray system. Rather than exposing an object uniformly, the exposure is adapted depending on the opacity of the object. Here we show an experiment on an anthropomorphic phantom that resulted in a dose saving of 30%.

X-ray fluoroscopy is widely used for image guidance during cardiac intervention. However, radiation dose in these procedures can be high, and this is a ...

Epidural Intracranial Pressure Measurement in Rats Using a Fiber-optic Pressure Transducer

Elevated intracranial pressure (ICP) is a significant problem in several forms of ischemic brain injury including stroke, traumatic brain injury and cardiac arrest. This elevation may result in further neurological injury, in the form of transtentorial herniation1,2,3,4, midbrain compression, neurological deficit or increased cerebral infarct2,4. Current therapies are often inadequate to control elevated ICP in the clinical setting5,6,7 . Thus there is a need for accurate methods of ICP measurement in animal models to further our understanding of the basic mechanisms and to develop new treatments for elevated ICP.
In both the clinical and experimental setting ICP cannot be estimated without direct measurement. Several methods of ICP catheter insertion currently exist. Of these the intraventricular catheter has become the clinical 'gold standard' of ICP measurement in humans8. This method involves the partial removal of skull and the instrumentation of the catheter through brain tissue. Consequently, intraventricular catheters have an infection rate of 6-11%9. For this reason, subdural and epidural cannulations have become the preferred methods in animal models of ischemic injury. 
Various ICP measurement techniques have been adapted for animal models, and of these, fluid-filled telemetry catheters10 and solid state catheters are the most frequently used11,12,13,14,15. The fluid-filled systems are prone to developing air bubbles in the line, resulting in false ICP readings. Solid state probes avoid this problem (Figure 1). An additional problem is fitting catheters under the skull or into the ventricles without causing any brain injury that might alter the experimental outcomes. Therefore, we have developed a method that places an ICP catheter contiguous with the epidural space, but avoids the need to insert it between skull and brain. 
An optic fibre pressure catheter (420LP, SAMBA Sensors, Sweden) was used to measure ICP at the epidural location because the location of the pressure sensor (at the very tip of the catheter) was found to produce a high fidelity ICP signal in this model. There are other manufacturers of similar optic fibre technologies13 that may be used with our methodology. Alternative solid state catheters, which have the pressure sensor located at the side of the catheter tip, would not be appropriate for this model as the signal would be dampened by the presence of the monitoring screw. 
Here, we present a relatively simple and accurate method to measure ICP. This method can be used across a wide range of ICP related animal models.

A novel technique to record the pressures within the skull is described. The minimally invasive method uses a fibre-optic pressure sensing system to accurately measure intracranial pressure (ICP) in anaesthetized rats without causing significant brain trauma. The technique may be used in a wide range of experimental models.

Elevated intracranial pressure (ICP) is a significant problem in several forms of ischemic brain injury including stroke, traumatic brain injury and ...

Intravital Microscopy of Monocyte Homing and Tumor-Related Angiogenesis in a Murine Model of Peripheral Arterial Disease

The therapeutic goal for peripheral arterial disease and ischemic heart disease is to increase blood flow to ischemic areas caused by hemodynamic stenosis. Vascular surgery is a viable option in selected cases, but for patients without indications for surgery such as progression to rest pain, critical limb ischemia, or major disruptions to life or work, there are few possibilities for mitigating their disease. Cell therapy via monocyte-enhanced perfusion through the stimulation of collateral formation is one of a few non-invasive options.
Our group examines arteriogenesis after monocyte transplantation into mice using the hindlimb ischemia model. Previously, we have demonstrated improvement in hindlimb perfusion using tetanus-stimulated syngeneic monocyte transplantation. In addition to the effects on the collateral formation, tumor growth could be affected by this therapy as well. To investigate these effects, we use a basement membrane-like matrix mouse model by injecting the extracellular matrix of the Engelbreth-Holm-Swarm sarcoma into the flank of the mouse, after occlusion of the femoral artery.
After the artificial tumor studies, we use intravital microscopy to study in vivo tumor-angiogenesis and monocyte homing within collateral arteries. Previous studies have described the histological examination of animal models, which presupposes subsequent analysis to post-mortem artifacts. Our approach visualizes monocyte homing to areas of collateralization in real time sequences, is easy to perform, and investigates the process of arteriogenesis and tumor angiogenesis in vivo.

Monocytes are important mediators of arteriogenesis in the context of peripheral arterial disease. Using a basement membrane-like matrix and intravital microscopy, this protocol investigates monocyte homing and tumor-related angiogenesis after monocyte injection in the femoral artery ligation murine model.

The therapeutic goal for peripheral arterial disease and ischemic heart disease is to increase blood flow to ischemic areas caused by hemodynamic ...

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated arc therapy (VMAT) plans for patients with head/neck cancer and 4-field box plans for patients with cervical cancer. It is a combination of specially developed in-house software that uses an application programming interface to communicate with a commercial radiotherapy treatment planning system. It also interfaces with a commercial secondary dose verification software. The necessary inputs to the system are a Treatment Plan Order, approved by the radiation oncologist, and a simulation computed tomography (CT) image, approved by the radiographer. The RPA then generates a complete radiotherapy treatment plan. For the cervical cancer treatment plans, no additional user intervention is necessary until the plan is complete. For head/neck treatment plans, after the normal tissue and some of the target structures are automatically delineated on the CT image, the radiation oncologist must review the contours, making edits if necessary. They also delineate the gross tumor volume. The RPA then completes the treatment planning process, creating a VMAT plan. Finally, the completed plan must be reviewed by qualified clinical staff.

Radiation therapy is a highly complex cancer treatment that requires multiple specialists to create a treatment plan and provide quality assurance (QA) prior to delivery to a patient. This protocol describes the use of a fully automated system, the Radiation Planning Assistant (RPA), to create high-quality radiation treatment plans.

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated ...

Predicting Treatment Response to Image-Guided Therapies Using Machine Learning: An Example for Trans-Arterial Treatment of Hepatocellular Carcinoma

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this study was to develop a method to predict response to intra-arterial treatment prior to intervention.
The method provides a general framework for predicting outcomes prior to intra-arterial therapy. It involves pooling clinical, demographic and imaging data across a cohort of patients and using these data to train a machine learning model. The trained model is applied to new patients in order to predict their likelihood of response to intra-arterial therapy.
The method entails the acquisition and parsing of clinical, demographic and imaging data from N patients who have already undergone trans-arterial therapies. These data are parsed into discrete features (age, sex, cirrhosis, degree of tumor enhancement, etc.) and binarized into true/false values (e.g., age over 60, male gender, tumor enhancement beyond a set threshold, etc.). Low-variance features and features with low univariate associations with the outcome are removed. Each treated patient is labeled according to whether they responded or did not respond to treatment. Each training patient is thus represented by a set of binary features and an outcome label. Machine learning models are trained using N - 1 patients with testing on the left-out patient. This process is repeated for each of the N patients. The N models are averaged to arrive at a final model.
The technique is extensible and enables inclusion of additional features in the future. It is also a generalizable process that may be applied to clinical research questions outside of interventional radiology. The main limitation is the need to derive features manually from each patient. A popular modern form of machine learning called deep learning does not suffer from this limitation, but requires larger datasets.

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. A method for predicting response to these therapies is proposed. The technique uses pre-procedural clinical, demographic, and imaging information to train machine learning models capable of predicting response prior to treatment.

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this ...

Radiation Treatment of Organotypic Cultures from Submandibular and Parotid Salivary Glands Models Key In Vivo Characteristics

Hyposalivation and xerostomia create chronic oral complications that decrease the quality of life in head and neck cancer patients who are treated with radiotherapy. Experimental approaches to understanding mechanisms of salivary gland dysfunction and restoration have focused on in vivo models, which are handicapped by an inability to systematically screen therapeutic candidates and efficiencies in transfection capability to manipulate specific genes. The purpose of this salivary gland organotypic culture protocol is to evaluate maximal time of culture viability and characterize cellular changes following ex vivo radiation treatment. We utilized immunofluorescent staining and confocal microscopy to determine when specific cell populations and markers are present during a 30-day culture period. In addition, cellular markers previously reported in in vivo radiation models are evaluated in cultures that are irradiated ex vivo. Moving forward, this method is an attractive platform for rapid ex vivo assessment of murine and human salivary gland tissue responses to therapeutic agents that improve salivary function.

Using three-dimensional organotypic cultures to visualize morphology and functional markers of salivary glands may provide novel insights into the mechanisms of tissue damage following radiation. Described here is a protocol to section, culture, irradiate, stain, and image 50&#8211;90 &#956;m thick salivary gland sections prior to and following exposure to ionizing radiation.

Hyposalivation and xerostomia create chronic oral complications that decrease the quality of life in head and neck cancer patients who are treated with ...

OP-IVM: Combining In vitro Maturation after Oocyte Retrieval with Gynecological Surgery

The use of in vitro maturation (IVM) before gynecological operation (OP-IVM) is an extension of conventional IVM that combines IVM following oocyte retrieval with routine gynecological surgery. OP-IVM is suitable for patients undergoing benign gynecological surgery who have the need for fertility preservation (FP) or infertility treatments such as in vitro fertilization and embryo transfer (IVF-ET). In the operating room, patients undergoing benign gynecological surgery are first anesthetized and receive ultrasound-guided immature follicle aspiration (IMFA) treatment. As the subsequent gynecological surgery is performed, the cumulus-oocyte complexes (COCs) are examined, and the immature COCs are transferred into the IVM medium and cultured for 28-32 hours in the IVF laboratory. After assessment, mature oocytes in the MII stage will be selected and cryopreserved in liquid nitrogen for FP or fertilized by intracytoplasmic sperm injection (ICSI) for IVF-ET. By combining IVM with gynecological surgery, immature oocytes that would have been discarded can be saved and used for assisted reproductive technology (ART). The procedure, significance and critical aspects of OP-IVM are described in this article.

In vitro maturation (IVM) before gynecological operation (OP-IVM) combines IVM following oocyte retrieval with routine gynecological surgery and serves as an extension of conventional IVM applications for fertility preservation.

The use of in vitro maturation (IVM) before gynecological operation (OP-IVM) is an extension of conventional IVM that combines IVM following oocyte ...

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 ...

Continuous Venous-Arterial Doppler Ultrasound During a Preload Challenge

A preload challenge (PC) is a clinical maneuver that, first, increases the cardiac filling (i.e., preload) and, second, calculates the change in cardiac output. Fundamentally, a PC is a bedside approach for testing the Frank-Starling-Sarnoff (i.e., "cardiac function") curve. Normally, this curve has a steep slope such that a small change in the cardiac preload generates a large change in the stroke volume (SV) or cardiac output. However, in various disease states, the slope of this relationship flattens such that increasing the volume into the heart leads to little rise in the SV. In this pathological scenario, additional cardiac preload (e.g., intravenous fluid) is unlikely to be physiologically effective and could lead to harm if organ congestion evolves. Therefore, inferring both the cardiac preload and output is clinically useful as it may guide intravenous (IV) fluid resuscitation. Accordingly, the goal of this protocol is to describe a method for contemporaneously tracking the surrogates of cardiac preload and output using a novel, wireless, wearable ultrasound during a well-validated preload challenge.

The Frank-Starling-Sarnoff curve is clinically important and describes the relationship between cardiac preload and output. This report illustrates a novel method of simultaneous jugular venous and carotid arterial Doppler velocimetry as transient surrogates of cardiac preload and output, respectively; this approach is enabled by wireless, wearable Doppler ultrasound.

A preload challenge (PC) is a clinical maneuver that, first, increases the cardiac filling (i.e., preload) and, second, calculates the change in cardiac ...

Optic Nerve Sheath Point of Care Ultrasound: Image Acquisition

The goal of this protocol is to develop a standardized method for acquiring images of the optic nerve sheath and measuring the optic nerve sheath diameter (ONSD). Diagnostic ultrasound of the ONSD to detect intracranial hypertension has traditionally faced many problems because of methodologic discrepancies. Due to inconsistencies in the measuring techniques, the potential for ONSD to become a non-invasive bedside monitoring tool for ICP has been hampered. However, establishing a transparent, consistent methodology for measuring the ONSD would support its use as a valid and reliable method of identifying intracranial hypertension. This is important as it has both high sensitivity and specificity in acute care settings. This narrative review describes ONSD POCUS image acquisition, including patient positioning, transducer selection, probe placement, the acquisition sequence, and image optimization. Further, visual aids are provided to assist in real-time during image acquisition. This method should be considered for patients for whom there are concerns regarding intracranial hypertension but who do not have an intracranial monitor in place.

Point-of-care ultrasound (POCUS) of the optic nerve sheath diameter (ONSD) has been shown to be useful in identifying patients with increased intracranial pressure (ICP). However, the non-standardized technique for this POCUS has hampered its use. We present a standardized image acquisition protocol for use in the acute care setting.

The goal of this protocol is to develop a standardized method for acquiring images of the optic nerve sheath and measuring the optic nerve sheath diameter ...