To decrease time duration of door-to-image, when a patient arrives at the ER, “Fast track” alert is to activate the stroke team for rapid neurologic assessment and the decision and acquisition of imaging modalities, and administration of intra-venous tPA to eligible patients. Fig. 2 shows the workflow from door to image and call to the endovascular neurosurgeon, interventional neurologist, and angio-suite technician and nurse. After ER doctor assess neurologic symptom of the patient, they simultaneously do a warm up call (the text message “Stroke Fast Track” is delivered to cell phone) to a neurosurgeon and neurologist, and send the patient to CT room. Before the transportation to CT room to minimize time delay, we prepare the intra-venous line route for tPA or anti-hypertensive drug administration, or for the consciousness sedation (CS) in advance. Usually, we tried to keep the Foley catheterization within 3-5 minutes. If a non-contrast brain CT show intracerebral hemorrhage, the patient will be transferred to neurosurgery. If brain CT show no hemorrhage, the neurologist will perform multi-phase CT Angiography for assessing intra-or extra-cranial artery and collateral status of occluded vessel [19]. At the time of the confirmation of LVO in multi-phase CT angiography, neurologist just called to endovascular neurosurgeon or interventional neurologist together with angioroom technician and nurse.

To decrease the time duration of image-to-puncture after the acquisition of CT or MR angiography, the next process may be necessary: 1) “no returns” to ER and direct transportation to angioroom, 2) operation the angio-suite in advance before the arrival of the patient, 3) pre-medication of CS to keep the patient from moving, and 4) preparation of sterile IAT kit including basic equipment earlier.

First, for “no returns” to ER, in the patient who is suggestive of embolic LVO, we do not prepare the L-tube in ER. However, in the patient who is suggestive of atherosclerotic intracranial stenosis, we prepare the L-tube for the oral administration of aspirin 300 mg and clopidogrel 325 mg, especially in the patient with low consciousness level. Second, it is important to minimize time delay to operate and prepare the angio-suite machine in advance. In the pre-IAT period, most of physicians cannot operate the angioroom machine, because the technician usually turns it on in advance. However, it is important for rapid procedure for anyone who visits angioroom for the first time to know how to turn on and prepare the angio-machine, because the technician or nurse does not always arrive at the hospital before the physician. And so, Fig. (3A and B) shows that anyone who first visit the angioroom do the same preparation for operating angio-suite and the easy way to turn it on is to make these serial pictures’ file on the desktop computer so that anyone who comes into the angioroom can see it (Fig. 3C). Third, the patient’s severe movement makes the procedure difficult and the time delay. So, we need to prepare dexmedetomidine (Precedex^®) as pre-medication for consciousness sedation in ER. To prevent sudden decrease of BP, it does not give loading dose, but gives maintenance dose. And so, it takes approximately 10 minutes for the patient to be sedated, we should begin the CS as soon as the patient arrives in angioroom. Also, for the rapid preparation of all device for endovascular procedure, the angio-room technicians prepare several sterile IAT kit including basic equipment such as syringes, 3-way check valves, flushing lines, 0.035 wire, and flushing lines, it can be especially helpful to decrease time duration in off-duty (Fig. 3D).

In the puncture-to-recanalization period, there are flowchart of the preparation of all devices for the endovascular procedure (Fig. 4) In the pre-IAT period, from the femoral sheath to thrombectomy devices (stent or reperfusion catheter), no standardized protocol for what instrument to use. We usually performed non-lesional (contralateral side ICA of occluded vessel and vertebral artery) and lesional (the side of occluded vessel) side angiography and then started the procedure for endovascular thrombectomy. And so, after the post-IAT period, standardized protocol is set for which instrument to use (Fig. 4A, B).

In the post-IAT setting, 9 F femoral sheath was placed in the femoral artery, and 9 F balloon-guiding catheter is used for direct access proximal to target occlusion site. 9 F balloon guiding catheter is usually placed on distal common carotid artery (CCA) or proximal internal carotid artery (ICA). A 5 F or 6 F intermediate catheter system (Sofia, Microvention, Tustin, CA, USA) was introduced and placed proximal to target artery. Through the intermediate catheter, retrievable stent (Solitaire FR, ev3, Irvine, CA, USA) was first tried during endovascular thrombectomy. The thrombus was placed within the center of total length of retrievable stent in consideration of no presence of stent strut to distal 5-10 mm of the proximal stent marker, the stent was deployed completely by pulling back the micro-catheter near proximal to the proximal stent marker. And then, angiography was performed to confirm the immediate flow restoration for adequate stent placement. From deployment to pullback of stent, it was left for about 5 minutes to allow the thrombus formation to be embedded within the stent. The Solitaire FR stent and the micro-catheter were pulled back simultaneously after inflating the balloon of balloon-guiding catheter (BGC). And then, regardless of the presence of clot retrieval in the stent strut, aspirations were performed two to three times with a 50 cc syringe to remove the floating thrombus that was cut off from the main thrombus and migrated to distal.

After the failure of recanalization with stent retriever, we tried penumbra reperfusion catheter. we placed the catheter just proximal to the clot occlusion site, and used the negative pressure at the proximal tip by continuous aspiration with a 50 mL syringe. Then, the catheter was carefully pulled back.

Also, we have made endovascular IAT protocol that includes detailed procedures according to the location of the occluded vessel, such as MCA and ICA. First, MCA protocol were as follows (Fig. 5). We divided the occlusion site into non-bifurcation vs. bifurcation type thrombus. Bifurcation type thrombus is usually located in distal M1 site involving the MCA bifurcation. This occlusion site (distal M1 occlusion) is high probability of embolic occlusion, and non-bifurcation occlusion (proximal M1 occlusion) is likely to be Intracranial artery stenosis (ICAS) (Fig. 5). To be suspicious of ICAS, Intra-arterial tirofiban (Aggrastat^®) infusion (0.5-1.5 mg) through the micro-catheter was achieved in just proximal portion of the occlusion site. In the patient refractory to tirofiban infusion, for the balloon angioplasty, Gateway^® percutaneous trans-luminal angioplasty (PTA) balloon (Stryker Neurovascular, Fremont, CA) was advanced and inflated very carefully through 0.014-inch exchange micro-wire (Transcend [Stryker Neurovascular, Natick, MA, USA]). Balloon was carefully inflated to near 80% of normal distal vessel. In the permanent stent deployment, intra-procedural loading with 300mg of aspirin and 325 mg of clopidogrel was initiated before the placement of rescue stenting.

In ICA protocol, the treatment process includes whether carotid artery stenosis (CAS) is present. When it is suggestive of carotid artery stenosis, suction thrombectomy with guiding catheter or intermediate catheter was performed to remove blood clots as possible. Balloon angioplasty is then performed in CAS, irrespective of carotid stenting. Usually, in the patients with ICA occlusion, remote or contact aspiration were first used with a reperfusion catheter for recanalization. And then, in the distal ICA occlusion, a combination of stents and reperfusion catheters was usually performed (Fig. 6).

The extent of recanalization was classified according to the Thrombolysis in cerebral infarction (TICI) grading scale. TICI grade 2b and 3 were successful recanalization, whereas TICI grades 0 to 2a were unsuccessful recanalization. 3-month follow-up scores were obtained by telephone follow-up or an outpatient visit by nursing practitioner. Baseline characteristics included age, gender, the location of occluded vessel in anterior circulation (M1, M2, and ICA). The outcomes were measured according to post-procedural TICI grade, the modified Rankin Score (mRS) scores at 3 months. The good and poor outcome of mRS score at 3 months were <2 and 3-6, respectively. And, we divided into two groups: prevs. post-IAT group. To assess the effectiveness of IAT protocol, we checked the time duration (min) in each three steps: 1) door-to-image, 2) image-to-puncture, and 3) puncture-to-recanalization, respectively.

Statistical analysis was performed with commercial software (SPSS, version 15.0, SPSS Inc., De, USA). The descriptive analysis for each data is presented as means±standard deviation. The Chi-square’s test was used for the statistical significance of the independent variables (Gender, age, the location of occluded vessel, successful recanalization TICI 2b-3, and good outcome mRS 0-2 at 3-month) between pre- and post-IAT groups. Also, independent t-test was used for the statistical significance to compare the time duration including 1) door-to-image, 2) image-to-puncture, and 3) puncture-to-recanalization between two groups. A p-value of less than 0.05 was considered significant.

The time duration from symptom onset to recanalization of occluded artery result in the clinical outcomes of patient with major arterial occlusion. Recent several trials have shown that median time duration from symptom onset to groin puncture was 212, 330, and 245 minutes in IMS III, MR RESCUE, and Synthesis expansion, respectively [3,5,12]. This mainly resulted from the use of older devices and delayed time duration from stroke onset to initiation of endovascular treatment. And so, endovascular thrombectomy showed the lower recanalization rate in acute stroke patients, that is suggested to be inferior to IV thrombolysis.

And, time duration of door to puncture and image to puncture mainly affect successful recanalization rate. It is reported that every additional hour from door to puncture and from imaging to puncture has the association with a 22% and 26% decrease in the odds of TICIJ 2b/3 successful recanalization,2) respectively. The most likely explanation is as follows: 1) thrombus modification (higher fibrin contents and more organized configuration of old thrombus compared to fresh thrombus), 2) strong adhesion of the thrombus within the vessel wall over time which makes entrapment and retrieval of the thrombus more difficult [6,14].

As mentioned above, when the suspected stroke patient arrived to ER, neurologist, interventional neurologist, and endovascular neurosurgeon receive warm up call message, which is called as “Stroke Fast Track”. This notification induces stroke team members to wait and prepare for possible EVT. According to a survey of stroke centers in the US, initial contact with a stroke team physician was made prior to image acquisition at 86% (25/29) of centers [10].

After the detection of no intracranial hemorrhage, rapid and non-invasive CT angiography (CTA) supply the important information on occluded vessel of the stenosis degree of extra- and intra-cranial vasculature. Currently, stroke guideline recommends CT/CTA to be an initial assessment of possible acute stroke patient [4,23]. We usually perform non contrast CT/Multiphase CT angiography within 6 hours and we check Brain MRI with MRA in the patient with symptom onset 6-24 hours. Although several imaging modalities is applied to suspected acute stroke patient, these imaging modalities should not delay intra-venous tPA infusion or endovascular thrombectomy [4,9]. Intra-venous tPA can be administered in the CT room immediately after making decision by stroke physician. We included several system in IAT protocol to decrease time duration in this door-to-image period, 1) rapid notification of suspected stroke patient arrived to ER to stroke team, 2) warm up call message, which is called as “Stroke Fast Track”, waiting and preparing for EVT, 3) Direct transportation to CT room, 4) rapid acquisition and administration of intra-venous line route for intra-venous tPA, consciousness sedation, and anti-hypertensive medication.

After the acquisition of brain imaging, the “no turn back” approach to ER is an important option to decrease door-to-puncture and image-to-puncture time eligible for EVT. To prevent no return from CT room to ER, we should get intra-venous line route in CT room. We should not return to ER for unnecessary L-tube insertion. If the L-tube insertion for aspirin plus clopidogrel medication is necessary for the process of EVT, we perform this procedure after the arrival in angioroom. And, in the aspect of iv-tPA administration, the patient who is eligible for EVT should be directly transported to the angio-suite without returning to the emergency room [1,24].

When door-to-image process is in progress from ER to CT room, it begins to prepare in angioroom simultaneously for the image-to-angioroom and angioroom-to-puncture. As the essential members of stroke team, there are angio-room technician and nurse, and they prepare the angiography suite for the EVT in advance [7]. This team-based approach resulted in a marked reduction in the treatment time duration and increase in the number of patients successfully treated in the American Heart Association’s Best Practice Strategies [15].

As shown in Fig. 3(D), a standardized IAT kit can be made and equipped in the angiography suite. This kit includes basic equipment such as variable sized syringes, trays, 3-way check valves, flushing lines, 9 F femoral sheath, 5 F angiography catheter and 0.035-inch guidewire, rotating hemostatic valves. This kit is helpful to decrease the time duration in angiography suite, especially in off-duty time. Previous paper reported that a standardized stroke kit, so called as BRISK (brisk recanalization ischemic stroke kit), was used for decreasing time duration in all processes [7].

In most cases of our stroke patient, we perform consciousness anesthesia (CS) to prevent the patient from moving in advance. And for CS, we use Precedex^®, which of loading dose can cause the blood pressure to drop suddenly, so we give it maintenance dose. Several studies reported that the use of CS has more benefits, such as in-hospital mortality, hospital costs, rate of pneumonia, and length of hospital stay, compared to general anesthesia (GA) [8,17]. However, recent randomized controlled studies shown that there was no difference between the use of CS and GA in neurologic outcomes 90 days after stroke [26]. In our opinion, CS has the following advantages: 1) It takes a short time to prepare, 2) neurological symptoms can be identified during the procedure, 3) anesthesia machine is not required. Whether it is consciousness or general anesthesia, it is better option to prepare rapidly according to the protocol made by each hospital.

We summarize several contents on workflow of this image-to-puncture period to decrease time duration, 1) not wait for the response of tPA, 2) the activation of stroke team eligible for EVT, 3) Rapid direct transportation from CT room to angiography-suite, 4) consciousness sedation rather than general anesthesia during the procedure, and 5) In-advance preparation of angiography-suite including the switch on of angio-machine, basic equipment, and all devices for EVT.