NADINE R. BARSOUM, M.D.; LAMIAA I.A. METWALLY, M.D. and IMAN M. HAMDY IBRAHIM, M.D.

Med. J. Cairo Univ., Vol. 84, No. 2, December: 175-183, 2016 www.medicaljournalofcairouniversity.net Peripheral Arterial Disease of the Lower Limbs: Is Doppler Examination as Efficient in its Diagnosis as Multi-Detector Computed Tomography Angiography (MDCTA)? NADINE R. BARSOUM, M.D.; LAMIAA I.A. METWALLY, M.D. and IMAN M. HAMDY IBRAHIM, M.D. The Department of Diagnostic and Intervention Radiology, Faculty of Medicine, Cairo University 175 The diagnosis of PAD and the treatment planning rely on clinical exam and non-invasive imaging [2]. High-quality, accurate imaging of the lower extremity vasculature is crucial for successful revascularization. Recent advances in imaging technology have significantly influenced the preoperative evaluation and management planning of patients with PAD [3]. Duplex ultrasonography (DUS) uses the combination of gray scale (B-mode) for vessel morphology and color pulsed-wave Doppler techniques. It is a safe, inexpensive technique that can provide functional information about vessel stenosis [4]. Duplex ultrasonography (DUS) can be used for management planning for lower extremity peripheral arterial disease (PAD), but has not replaced contrast-enhanced imaging such as computed tomography angiography (CTA) [5]. When duplex ultrasound provides inadequate information, non-invasive 3D imaging is the technique of choice in evaluating patients for limb salvage procedures and can then serve as a useful adjunct for surveillance [3]. In the last decade with the advent of MDCT, significant advantages were achieved, mainly the short scanning time, thin slice thickness and high spatial resolution, enabling the development of 3D reformatted images allowing the evaluation of different pathologies in the peripheral arteries [6,7]. Thereby, it has been possible to image with high-resolution the entire arterial tree using a single acquisition and a single injection of contrast media. MDCTA have shown to be reliable in the evaluation of occlusion pathologies in the arteries of the lower

176 Peripheral Arterial Disease of the Lower Limbs extremity and its clinical use is now increasing [7,8]. The aim of this study is to detect whether Doppler examination is as efficient as multi-detector computed tomography angiography in diagnosis of the different forms of peripheral arterial disease of the lower limbs. Patients and Methods This study included 40 patients (34 males and 6 females), they ranged in age from 44 to 87 years (their mean is 60.9 and average age were 60.8±11.6 years) and were prospectively recruited for this study who presented to the Vascular Surgery Clinic and Radiology Department, Cairo University Hospitals during the period from January 2013 to March 2015. All patients were clinically diagnosed with lower limb ischemia. All patients were diabetic, 38 were hypertensive and 7 had hyperlipidemia. All patients included in this study were subjected to arterial Doppler examination prior to computed tomography angiography. These studies were performed after the approval of the scientific and ethics committee of the hospital. CTA Technique: A 64-multi-detector row CT scanner (Toshiba 64; Aquilion) was used for evaluation of all patients. The patient should be fasting for at least 4 hours prior to the examination. Renal function laboratory tests were requested before the examination to rule out renal impairment. Patients were taught how to hold breath during examination when requested, to ensure their cooperation. The patient lies on the CT table in the supine position followed by injection of 100-120ml of non-ionic contrast medium (Ultravist) intravenously with a power injector using 320psi pressure, at 4mm/sec rate. The CT angiographic acquisition parameters were: Tube voltage: 120kV; effective tube flow: 250mAs, rotation time: 0.4sec, table speed: 29mm/s; pitch: 0.844mm; section thickness: 0.5mm, and reconstruction interval: 0.5-1mm. Routinely, scanning started from the descending aorta at D10 level through the toes, to evaluate the entire inflow and runoff. A region of interest (ROI) is applied on the descending aorta at this level. After the injection of low-dose contrast material, scanning was automatically started when the density in the abdominal aorta reached the level of 180 HU. Because the device can only process 1500 sections, the scanning was realized in two stages. In the first stage, the abdominal aorta and above the knee level, and in the second stage, the area between the below-the-knee and the tip of the foot were evaluated. Evaluation of the images: The CT images obtained were transferred onto the work-station, and the data were processed by using maximum intensity projection (MIP), multiplanar reformatting (MPR), CPR (curved multiplanar), and volume rendering (VR) techniques. All the arterial segments, particularly the axial segments, were studied based on MPR (multiplanar reformat) images. MIP and VR reconstructions were formed by removing the bone structures semiautomatically and using the 3D function of the work-station. Doppler study technique: Color Doppler sonography examinations were done using PHILLIPS-ATL; HDI 5000, which can combine a real time B-mode imaging system with pulsed and continuous wave Doppler facilities together with the availability of color coding of signals. The patients were instructed to fast for six hours prior to examination and avoid eating colonic gas forming food e.g. dairy products, to facilitate examination of the aorto-iliac vessels. Patients were examined in the supine position. Beginning at the aortic bifurcation, a 3.5MHz probe was used to examine the aorta, common, and external iliac arteries. A 7.5MHz probe was sometimes used in well prepared thin patients. Both common femoral arteries were examined using a 7.5MHz probe with the limb under examination slightly abducted and externally rotated for better scanning of the femoral artery. Same probe was used in examining the popliteal and infrapopliteal arteries. Each segment was examined first by B-mode for detection of atheromatous plaques and wall calcifications then by color flow imaging transversely and longitudinally to size the colored flow in the lumen with respect to the arterial wall and to detect areas of flow disturbance, increased velocity, and jets. The transducer was transverse to the arterial segment with 30º angulation to the vertical plane to encode the arterial color signal. Then longitudinal scanning was performed for placing the Doppler sample gate in the lumen and correcting the angle cursor parallel to the flow in

Nadine R. Barsoum, et al. 177 the lumen to obtain the Doppler spectrum and calculation of peak systolic velocity (PSV). The color scale was set for about 30cm/sec maximal mean velocity. The overall gain was increased until color noise appeared in the static tissues adjacent to the arterial wall then the gain was gradually decreased until tissue noise just disappeared. The Doppler angle formed by the pulsed Doppler beam and the angle cursor, was kept around 60º. The angle cursor was adjusted to follow the axis of the blood flow visualized by color Doppler flow imaging. The smallest available sample volume was placed in the midstream of the visualized flow. The peak systolic velocity (PSV) was recorded from all the examined segments and in any area of suspected stenosis, values were recorded immediately before, within, and just distal to the stenosis. Occlusions were diagnosed when no color flow or Doppler spectral signal was detected in the segment inspite of the attempts to maximize the sensitivity for slow flow detection by increasing Doppler gain, decreasing the scale, and increasing the sample volume size. Results The study included 40 patients (34 males and 6 females) diagnosed with lower limb arterial lesions of different forms. Their mean is 60.9 and average age were 60.8±11.6 years. Twenty-one of the patients were smokers (10 of them were heavy smokers). All the patients were diabetic with a range from 10-30 years duration, with a mean duration of 18.5±6 years; and 38 were hypertensive for a duration 5-30 years, with a mean duration of 16.2±0.4 years. Seven patients had hyperlipidemia. Seven patients complained of unilateral lower limb pain, 8 complained of bilateral lower limb pain, 4 patients had bluish discoloration of the limb, 1 patient had a foot ulcer, 9 with ischemic pain, 6 had diabetic foot, 3 patients had aortic aneurysms and 2 patients had previous femoropopliteal grafts. Most of the patients were diagnosed with multiple arterial pathologies in one or both lower limbs. The pathologies were divided into attenuation (n=32), stenosis (n=22) and occlusion (n=30). The CTA was considered as the gold standard by which we evaluated the Doppler results. Table (1): Number of cases and accuracy of different types of lesions detected by Doppler. Lesions detected by Doppler Number of cases Accuracy Attenuation 25 83% Stenosis 17 88% Occlusion 17 68% We then divided the lesions according to the segments affected in the lower limb arterial tree to show the ability of the Doppler examination in detection of the segmental lesions in comparison to the CTA (Figs. 1,2,3). None of the thigh arterial segmental stenotic or attenuation lesions were detected by the Doppler: Common iliac artery [total length stenosis (n=3)] (Fig. 2); External iliac artery [segmental stenosis (n=1) and attenuation (n=1)] (Fig. 1); Common femoral artery [total stenosis (n=2) and attenuation (n=1)]. Three cases of complete occlusion of the CFA were detected by both CTA and Doppler studies; and one case of occlusion of EIA was diagnosed by both modalities; while one of the cases diagnosed as stenosis of the EIA was falsely diagnosed as occlusion by the Doppler examination. The stenotic lesions in the leg arteries were divided into: Superficial femoral artery [segmental (n=15) and whole length (n=4)] (8 segments were detected by Doppler, with a sensitivity of 53% and a negative predictive value of 47%) and all 4 segments of the whole length stenosis were detected by Doppler, with a sensitivity of 100%) (Figs. 1,2). Popliteal artery [segmental (n=5) and whole length (n=2)] (4 segments were detected by Doppler, with a sensitivity of 40% and a negative predictive value of 60%) and 4 segments (2 false positive) of the whole length stenosis were detected by Doppler, with a sensitivity of 100% and a positive predictive value of 50%). Posterior tibial artery [segmental (n=2) and whole length (n=4)] (1 segment was detected by Doppler, with a sensitivity of 50% and a negative predictive value of 50%) and 8 segments (4 false positives) of the whole length stenosis were detected by Doppler, with a sensitivity of 100% and positive predictive value of 50%).

178 Peripheral Arterial Disease of the Lower Limbs Anterior tibial artery [segmental (n=2) and whole length (n=7)] (1 segment was detected by Doppler, with a sensitivity of 50% and a negative predictive value of 50%) and 8 segments (1 false positive) of the whole length stenosis were detected by Doppler, with a sensitivity of 100% and positive predictive value of 88%. Peroneal artery [segmental (n=2) and whole length (n=6)] (1 segment was detected by Doppler, with a sensitivity of 50% and a negative predictive value of 50%) and 8 segments (2 false positives) of the whole length stenosis were detected by Doppler, with a sensitivity of 100% and positive predictive value of 75%. Ankle arteries [segmental (n=1) and whole length (n=3)] (1 segment was detected by Doppler, with a sensitivity of 100%) and 8 segments (5 false positives) of the whole length stenosis were detected by Doppler, with a sensitivity of 100% and positive predictive value of 38%. The occlusive lesions in the leg arteries were divided into: Superficial femoral artery [segmental (n=12) and whole length (n=2)] (10 segments were detected by Doppler, with a sensitivity of 83% and a negative predictive value of 17%) and 4 segments of the whole length occlusion were detected by Doppler (2 false positives), with a sensitivity of 100% and a PPV of 50% (Figs. 1,3). Popliteal artery [segmental (n=6) and whole length (n=2)] (2 segments were detected by Doppler, with a sensitivity of 33% and a negative predictive value of 67%) and 4 segments (2 false positive) of the whole length occlusion were detected by Doppler, with a sensitivity of 100% and a positive predictive value of 50%. Posterior tibial artery [segmental (n=14) and whole length (n=7)] (3 segment was detected by Doppler, with a sensitivity of 21% and a negative predictive value of 67%) and 3 segments of the whole length occlusion were detected by Doppler, with a sensitivity of 43% and a negative predictive value of 57%. Anterior tibial artery [segmental (n=25) and whole length (n=5)] (5 segments were detected by Doppler, with a sensitivity of 20% and a negative predictive value of 80%) and 4 segments of the whole length occlusion were detected by Doppler, with a sensitivity of 80% and negative predictive value of 20%. Peroneal artery [segmental (n=8) and whole length (n=4)] (2 segments were detected by Dop- pler, with a sensitivity of 25% and a negative predictive value of 75%) and 1 segment of the whole length occlusion was detected by Doppler, with a sensitivity of 25% and negative predictive value of 75%. Ankle arteries [segmental (n=3) and whole length (n=2)] (2 segments were detected by Doppler, with a sensitivity of 67% and negative predictive value of 33%) and 2 segments (1 false positive) of the whole length occlusion were detected by Doppler, with a sensitivity of 100% and positive predictive value of 38%). The cases of arterial attenuation in the leg arteries were divided into: Superficial femoral artery [segmental (n=2) and whole length (n=1)] (1 segment was detected by Doppler, with a sensitivity of 50%) and the whole length attenuation was not detected by Doppler, with a sensitivity of 0%. No cases with attenuation of the popliteal artery were diagnosed in this study. Posterior tibial artery [segmental (n=8) and whole length (n=15)] (5 segment was detected by Doppler, with a sensitivity of 63% and a negative predictive value of 38%) and 35 segments of the whole length attenuation were detected by Doppler (20 false positive cases), with a sensitivity of 100% and a positive predictive value of 43% (Fig. 3). Anterior tibial artery [segmental (n=21) and whole length (n=18)] (4 segments were detected by Doppler, with a sensitivity of 19% and a negative predictive value of 86%) and 36 segment of the whole length attenuation was detected by Doppler (18 false positive cases), with a sensitivity of 100% and positive predictive value of 50% (Figs. 1-3). Peroneal artery [segmental (n=9) and whole length (n=20)] (4 segments were detected by Doppler, with a sensitivity of 44% and a negative predictive value of 56%) and 35 segments of the whole length attenuation were detected by Doppler (15 false positive), with a sensitivity of 100% and negative predictive value of 57%. Ankle arteries [segmental (n=1) and whole length (n=14)] (4 segments were detected by Doppler (3 false positives), with a sensitivity of 100% and negative predictive value of 25%) and 36 segments (22 false positives) of the whole length attenuation were detected by Doppler, with a sensitivity of 100% and positive predictive value of 39%.

Nadine R. Barsoum, et al. 179 (A) (B) (C) (D) (E) (F) Fig. (1): (A-G): Male diabetic and hypertensive patient, 61 years old, complaining from severe pain in the left leg. (A,B): MIP images, (C-E): Axial images, (F,G): color-coded Doppler images. (A) : Stenosis of the middle third of the right SFA. (A) : Stenotic segment 3cm from the origin of the left EIA (long arrow). (B) : Another focal stenotic segment 5.5cm from its origin with attenuated distal aspect (black arrow). (B,D): Two stenotic segments 4.6cm and 14cm from the origin of the left SFA. Distal occlusion of the middle third of the left SFA 3.8cm long (wavy arrow). (A,E): Attenuated proximal third of the left ATA (curved arrow). (F) : Color-coded Doppler image showing post stenotic markedly damped velocity (10.5cm/sec) in the left SFA. (G) : Color-coded Doppler image showing total luminal occlusion of the middle third of the left SFA. (G)

180 Peripheral Arterial Disease of the Lower Limbs (A) (B) (C) (D) (E) Fig. (2): (A-E): Female diabetic patient 75 years old complaining from severe bilateral lower limb pain. CTA of the lower limbs. (A): VR image, (B,C): MIP images, (D,E): Axial images. (A) : Significant stenotic lesion at the proximal right CIA 1.1 cm from the aortic bifurcation 9mm long and 66% reduction of its lumen (white arrow). (B) : Multiple stenotic segments of variable degrees mounting to total occlusion along the course of the right SFA (more at the proximal 1/3) causing a beaded outline (long white thin arrows). (C) : Marked attenuation of the distal 1/3 of the right ATA with re-opacified dorsalis pedis (wavy arrow). (C,E) : Marked attenuation of the proximal 1/3 of the left ATA with total occlusion at the rest till the ankle as the dorsalis pedis refill through collaterals from the peroneal artery (curved arrow). (B,D): Multiple diffuse mural irregularities and short stenotic segments of the left SFA, the most evident one (3mm long) of total occlusion (black arrow) with good collateral refilling is seen 21cm above the knee level.

Nadine R. Barsoum, et al. 181 (A) (B) (C) (D) (E) Fig. (3): (A-E): Male diabetic patient 72 years old. Complaining from claudication pain on both lower limbs. Doppler showed left SFA occlusion and right SFA stenosis. CTA of the lower limbs. (A): Volume rendered image (VR), (B): Maximum intensity projection image (MIP), (C-E): Axial images. (A) : Diffuse atherosclerotic changes and atheromatous mural calcification of both lower limb vessels. (B,C): Total occlusion of the right SFA few cm below its origin from the CFA followed by collateral refilling of the popliteal artery (black arrow). (B,D): Marked attenuation of the proximal right ATA and PTA with near total distal occlusion (wavy black arrows). (B,E): Almost total occlusion of the left tibio-peroneal trunk with collateral refilling of the middle third of the peroneal and PTA which are seen markedly attenuated with multiple stenotic segments (curved black arrow).

182 Peripheral Arterial Disease of the Lower Limbs Discussion Peripheral arterial disease carries the risk of limb loss, hence thorough evaluation of these patients should be done by a complete history and physical examination in addition to non-invasive imaging studies including duplex ultrasonography and CT angiography. High quality, accurate imaging of the lower limb vessels is mandatory for successful revascularization of diseased vessels. In the recent past, digital subtraction angiography was considered as the traditional gold standard, however with the improvement of imaging technology high-quality alternatives such as computed tomography angiography (CTA), magnetic resonance angiography (MRA) and intraoperative imaging, (intravascular ultrasound, cone beam CT and CO2 angiography) [3]. Ultrasound is an excellent option for surveillance of lower extremity bypasses and is known to be predictive of patency. In patients in need of limb salvage procedures, non-invasive 3D imaging is the technique of choice, especially when duplex ultrasound provides inadequate information. CT angiography has become the preferred technique for most vascular surgeons [9]. In our study Doppler ultrasound detected attenuation of the arteries with an accuracy of 83%; arterial stenosis with accuracy of 88% and arterial occlusion with an accuracy of 68%. The overall sensitivity of Doppler ultrasound in the diagnosis of hemodynamically significant lesions in the superficial femoral arteries was 77% in stenotic lesions; 92% in occlusive lesions and 50% of cases of arterial attenuation. These results were more or less in concurrence with those seen in the study done by Pollack, et al., in 2012, which stated that the accuracy of ultrasound in detection of stenosis of the aortic, iliac and superficial femoral arteries was 89%. On the other hand, the average sensitivity of Doppler in the diagnosis of lesions of the peripheral arteries was 79% in stenotic lesions; 51% in cases of occlusion and 80% in cases of arterial attenuation. These results were slightly lower than those seen in the study done by Pollack et al., in 2012, which showed a pooled sensitivity of 88% for duplex U/S in detection of PAD. Conclusion: The major guidelines (TASC II, ESC and ACC/ AHA) support the use of either Doppler, CTA or MRA depending upon patient specific factors, local expertise and safety profile. Compared to our gold standard examination MDCT angiography of the lower limbs, we conclude that Doppler ultrasound with its lower cost and easy availability can be used as a screening technique for lower limb diseases; however, it cannot be relied upon in the pre-operative assessment of the disease, and will ultimately need the conjunction with another imaging modality for accurate diagnosis. References 1- GARCIA L.A.: Epidemiology and pathophysiology of lower extremity peripheral arterial disease. Journal of Endovascular Therapy, 13: 113-119, 2006. 2- CHAN D., ANDERSON M.E. and DOLMATCH B.L.: Imaging Evaluation of Lower Extremity Infra-inguinal Disease: Role of the Noninvasive Vascular Laboratory, Computed Tomography Angiography, and Magnetic Resonance Angiography. Tech. Vasc. Interv. Radiol., 13: 11-22, 2010. 3- DURAN C. and BISMUTH J.: Advanced Imaging in Limb Salvage Methodist Debakey Cardiovasc J. Oct- Dec., 8 (4): 28-32, 2012. 4- NORGREN L., HIATT W.R., DORMANDY J.A., NE- HLER M.R., HARRIS K.A. and FOWKES F.G.: On behalf of the TASC II Working group. Inter-society consensus for the management of peripheral arterial disease (TASC II) J. Vasc. Surg., 45: S5-S67, 2007. 5- De VOS M.S., BOL B.J., GRAVEREAUX E.C., HAM- MING J.F. and NGUYEN L.L.: Treatment planning for peripheral arterial disease based on duplex ultrasonography and computed tomography angiography: Consistency, confidence and the value of additional imaging. Surgery, 156 (2): 492-502, 2014. 6- HIATT M.D., FLEISCHMANN D., HELLINGER J.C. and RUBIN G.D.: Angiographic imaging of the lower extremities with multi-detector CT. Radiologic Clinics of North America, 43: 1119-1127, 2005. 7- OZTEKIN P.S., SONMEZ A., KUCUKAY F., OZTUNA D., SANLıDILEK U. and KOSAR U.: An evaluation of the arterial occlusions in peripheral arterial disease by 64-detector multi-slice CT angiography: DSA correlation. World Journal of Cardiovascular Diseases, 3: 250-256, 2013. 8- FLEISCHMANN D., HALLETT R.L. and RUBIN G.D.: CT Angiography of Peripheral Arterial Disease. J. Vasc. Interv. Radiol., 17: 3-26, 2006. 9- POLLAK A.W., NORTON P. and KRAMER C.M.: Multimodality Imaging of Lower Extremity Peripheral Arterial Disease: Current Role and Future Directions. Circ. Cardiovasc. Imaging, Nov. 1; 5 (6): 797-807, 2012.

Nadine R. Barsoum, et al. 183