Evaluation of indium-111-labeled antifibrin monoclonal antibody for the diagnosis of venous thrombotic disease

The potential advantage of using 111In-antifibrin (111In-AF) monoclonal antibody for the diagnosis of deep venous thrombosis (DVT) was studied in 44 patients with suspected DVT (27 underwent heparin therapy before 111In-AF injection). All patients had contrast venography (considered as the gold standard) and 111In-AF scintigraphy within 24 hr. Two to 3 mCi of 111In-AF were injected intravenously, and planar scintigraphy of the limbs was recorded within 10 min (17 times), 3 hr (44 times), and 18 hr (39 times). Indium-111-AF images were then interpreted without knowledge of the results of the other examinations. The DVT diagnostic accuracy of 111In-AF was greater when interpretation was based on images recorded at different time periods after injection. Indium-111-AF sensitivity for diagnosis of DVT was 85% (29/34) and was not apparently decreased by heparin therapy. None of the 10 patients with negative contrast venography had a positive 111In-AF scan. The results demonstrate the importance of recording serial images and the excellent accuracy of 111In-AF for diagnosing DVT.     

Evaluation of a 3-hour indium-111 leukocyte image as a surrogate for a technetium-99m nanocolloid marrow scan in the diagnosis of orthopedic infection

OBJECTIVES: This is a retrospective study to evaluate a 3-hour In-111-labeled leukocyte image as a surrogate for a Tc-99m nanocolloid marrow scan in the investigation of suspected orthopedic infection using In-111 leukocyte scintigraphy. METHODS: Images from 51 patients who had received contemporaneous In-111-labeled leukocyte scintigraphy and Tc-99m nanocolloid marrow scintigraphy were reviewed. Initially, the 3-hour and 22-hour In-111-labeled leukocyte images were compared. Sites of abnormal uptake on the 22-hour image were correlated with the 3-hour image and were graded according to the level of concordance or discordance. One week later, the Tc-99m nanocolloid images and 22-hour In-111-labeled leukocyte images of the same patients were compared and graded for concordance or discordance. When discrepancies in grading arose between the observers, a consensus opinion was achieved after additional review of the images a week later. RESULTS: On inspection of the 22-hour In-111 leukocyte images, 93 sites of focal, potentially abnormal leukocyte accumulation were identified. When the grading system was reduced to simply "concordant" or "discordant," there was good agreement between the observers in the majority of cases, with kappa statistics 0.77 for Tc-99m nanocolloid versus 22-hour In-111-labeled leukocyte images and 0.78 for 3-hour versus 22-hour In-111-labeled leukocyte images. Using the comparison of the Tc-99m nanocolloid marrow scan and the 22-hour In-111-labeled leukocyte images to identify concordance or discordance as the "gold standard" for scintigraphic evaluation of suspected orthopedic infection, comparison of the 3-hour In-111-labeled leukocyte images with the 3-hour In-111-labeled leukocyte images gave a sensitivity of 77%, a specificity of 77%, and an accuracy of 77%. CONCLUSIONS: A 3-hour image is helpful using In-111-labeled leukocyte scintigraphy.     

Indium-111 labeled purified granulocytes in the diagnosis of synthetic vascular graft infection

Indium-111 labeled leukocytes have been shown to be useful in the diagnosis of synthetic vascular graft infection. To minimize the potential effects of labeled red blood cells and platelets on image interpretation, the authors prepared purified autologous granulocytes (PG) from 84 ml of blood using Volex enhanced gravity sedimentation and Ficoll-Hypaque double density centrifugation. The labeling efficiency of PG with In-111 tropolone was 90 +/- 9% (mean +/- SD). Imaging was performed 18-24 hours following injection of approximately 445 microcuries of In-111 PG in 26 patients with suspected infection of vascular grafts that had been implanted 12 days to 12 years prior to the study. In ten patients with proven graft infection, seven had positive In-111 PG scans. Ten of 11 patients without infection had negative scans. In five patients with clinically equivocal findings, scan results were positive in one, negative in one, and equivocal in three. A false-positive scan occurred in a patient with an uninfected inflammatory pseudoaneurysm of an aortic graft. These results confirm an earlier report that In-111 PG imaging is a useful technique in the diagnosis of synthetic vascular graft infection.     

Diagnostic value of the combination of echography-plethysmography in deep venous thromboses of the legs

The association of two non invasive methods: real time ultrasonography and plethysmography was studied prospectively for the diagnosis of deep vein thrombosis (DVT) in 70 patients. Their results were compared to contrast venography considered to the reference procedure. Venography showed DVT in 32 patients. Ultrasonography had a sensitivity of 69% and a specificity of 98%. The false negative results were related to iliac or calf vein thrombosis. Plethysmography had lower results than US (Se = 57%, Sp = 90%). In this study the sensivity of the two methods, either isolated or associated was not sufficient to allow their substitution to venography. Their association in all cases did not give better results than US alone. Because of its high specificity US can be performed first in cases of suspicion of DVT, especially in high risk patients. Plethysmography seems not to be necessary for the diagnosis.     

Isolated calf vein thrombosis: comparison of MR venography and conventional venography after initial sonography in symptomatic patients.

RATIONALE AND OBJECTIVES: The authors performed this study to compare magnetic resonance (MR) venography and conventional venography in the diagnosis of deep venous thrombosis (DVT) in the calf after sonography. MATERIALS AND METHODS: Sonography was performed in 595 patients who were suspected of having lower-extremity DVT. Patients with positive above-knee duplex sonograms, allergy to iodinated contrast material, renal insufficiency, or cardiac pacemakers and patients who were obese were excluded. The remaining 73 patients were asked to undergo MR venography and conventional venography. All studies were to be performed within 48 hours of the clinical diagnosis and according to standard clinical practice. Images were interpreted by radiologists who were blinded to the results of other modalities. Two separate analyses were performed: one in which conventional venography was used as the standard of reference, and one in which the presence of at least two positive studies for thrombus was considered diagnostic. RESULTS: Although 36 patients agreed to participate in the study, only 14 underwent MR venography and conventional venography within 48 hours of the clinical diagnosis. With use of any two positive studies for confirmation, acute DVT was diagnosed in three patients. Conventional venography depicted two of the three cases, whereas sonography and MR venography each depicted all three. The findings were concordant in only five of the 14 patients. CONCLUSION: Moderate discrepancy among modalities was demonstrated. This suggests radiologists should undertake comparisons among these three modalities for the detection of calf DVT. In patients with a high clinical suspicion, a second modality may be useful if the initial study is negative.     

Venous thrombosis: a controlled study on the performance of scintigraphy with 99Tcm-HMPAO-labelled platelets versus venography.

Thirty-three patients with symptoms and signs of a deep venous thrombosis (DVT) were examined by contrast venography and radionuclide imaging with 99Tcm-hexamethylpropyleneamineoxime (99Tcm-HMPAO)-labelled autologous platelets. There were 13 patients on heparin therapy and 20 without anticoagulation during the scintigraphy. Scintigraphy consisted of blood pool imaging at 5 to 20 min and accumulation imaging at 2, 4-6 and 18-24 h. In scintigraphy a positive finding was either a defect of radioactivity in the immediate blood pool phase or a hot spot indicative of accumulation of platelets in later phases. Fifteen out of 23 patients positive by venography were also positive by scintigraphy. Five of the eight false negative patients were on heparin treatment, two probably had DVT which were not quite fresh. The venography negative patients were also negative on scintigraphy. Nine out of 12 patients without anticoagulation had positive platelet accumulation compared with two out of 11 patients on heparin therapy. This difference was statistically significant (P less than 0.025). The sensitivity and specificity of platelet scintigraphy were 65 and 100%, respectively, in all patients and 83 and 100% in patients without anticoagulation. Our results suggest that scintigraphy with 99Tcm-HMPAO-labelled platelets is a useful alternative in diagnosing DVT in patients in whom a standard contrast X-ray venograph is contraindicated or otherwise unsuccessful.     

Acute thromboscintigraphy with (99m)Tc-apcitide: results of the phase 3 multicenter clinical trial comparing 99mTc-apcitide scintigraphy with contrast venography for imaging acute DVT. Multicenter Trial Investigators.

(99m)Tc-apcitide (formerly known as (99m)Tc-P280) is a radiolabeled peptide that binds with high affinity and specificity to the glycoprotein IIb/IIIa receptors expressed on the activated platelets that are involved in acute thrombosis. The purpose of the phase 3 multicenter clinical trials was to compare (99m)Tc-apcitide scintigraphy with contrast venography for imaging acute deep venous thrombosis (DVT). METHODS: A total of 280 patients were enrolled in 2 clinical trials conducted in North America and Europe. Patients were to be within 10 d of onset of signs and symptoms of acute DVT or within 10 d of surgery associated with a high risk of DVT. (99m)Tc-apcitide scintigraphy and contrast venography were to be performed within 36 h. Planar scintigraphic images were obtained at 10, 60, and 120-180 min after injection. (99m)Tc-apcitide scintigrams and contrast venograms were read with masking and also by the institutional investigators. RESULTS: Of a total of 243 patients who were evaluable, 61.7% were receiving heparin at the time of imaging. Masked reading of (99m)Tc-apcitide scintigraphy, compared with masked reading of contrast venography, had a sensitivity, specificity, and agreement of 73.4%, 67.5%, and 69.1%, respectively, which met the prospectively defined target efficacy endpoint in both trials. Institutional reading of (99m)Tc-apcitide scintigraphy, compared with institutional reading of contrast venography, had a sensitivity, specificity, and agreement of 75.5%, 72.8%, and 74.0%, respectively. However, the entire trial population included patients with a history of DVT who may have had old, nonacute venous thrombi that could confound the venography results. Therefore, data from patients having no history of DVT or pulmonary embolism and who presented within 3 d of onset of signs and symptoms (n = 63), i.e., patients for whom a venogram would be expected to be positive only if acute DVT were present, also were analyzed as a subset. In these patients, institutional reading of (99m)Tc-apcitide scintigraphy, compared with institutional reading of contrast venography, had a sensitivity, specificity, and agreement of 90.6%, 83.9%, and 87.3%, respectively. CONCLUSION: (99m)Tc-apcitide scintigraphy is a new diagnostic modality that is highly sensitive for imaging acute DVT.     

Deep venous thrombosis of extremities: role of MR imaging in the diagnosis

Current noninvasive imaging techniques for diagnosis of deep venous thrombosis (DVT) of extremities are limited in their ability to demonstrate central vein involvement and to distinguish acute from chronic changes. The utility of spin-echo magnetic resonance (MR) imaging for DVT was evaluated in 100 patients suspected of having either upper- (n = 25) or lower-extremity (n = 75) DVT. Ninety-seven patients were imaged successfully. In a subset of 36 patients, prospective comparison of MR imaging with contrast venography revealed a sensitivity of 90%, specificity of 100%, and Kappa level of agreement of .752 (P less than .0001). MR imaging showed more central extent of thrombus than did venography in all five patients with upper-extremity DVT and in 13 of 25 patients (52%) with lower-extremity DVT. Although all patients in the study were evaluated for acute symptoms, 13 of 59 (22%) MR imaging studies positive for DVT demonstrated chronic disease. MR images demonstrated ancillary abnormalities in 18 of 41 (44%) patients who did not have DVT. Thus, MR imaging has a role as the definitive examination when the results of initial screening studies are unsatisfactory, or as a first-line examination if (a) there is suspicion of upper-extremity or pelvic vein thrombosis, (b) there is a history of prior DVT that necessitates distinction of acute from chronic changes, or (c) other tests are unavailable.     

Computer assisted strain-gauge plethysmography is a practical method of excluding deep venous thrombosis

AIM: To evaluate a computed strain-gauge plethysmograph (CSGP) as a screening tool to exclude above knee deep venous thrombosis (DVT). METHODS: The first phase took place in the Radiology department. One hundred and forty-nine patients had both Doppler ultrasound and CSGP performed. Discordant results were resolved by venography where possible. The second phase took place in an acute medical admissions ward using a modified protocol. A further 173 patients had both studies performed. The results were collated and analysed. RESULTS: Phase 1. The predictive value of a negative CSGP study was 98%. There were two false-negative CSGP results (false-negative rate 5%), including one equivocal CSGP study which had deep venous thrombosis on ultrasound examination. Two patients thought to have thrombus on ultrasound proved not to have acute thrombus on venography. Phase 2. The negative predictive value of CSGP using a modified protocol was 97%. There were two definite and one possible false-negative studies (false-negative rate 4-7%). CONCLUSION: Computer strain-gauge plethysmograph can provide a simple, cheap and effective method of excluding lower limb DVT. However, its use should be rigorously assessed in each hospital in which it is used. Goddard, A. J. P., Chakraverty, S. & Wright, J. (2001). Clinical Radiology56, 30-34.     

联合应用多层螺旋CT肺动脉造影和间接CT静脉造影诊断静脉血栓栓塞症

目的探讨联合应用多层螺旋CT肺动脉造影（MSCTPA）和间接CT静脉造影（CTV）诊断静脉血栓栓塞症（VTE）的价值。资料与方法对临床疑似VTE的87例患者,联合应用MSCTPA和间接CTV进行检查,在胭静脉至股总静脉水平,比较间接CTV与多普勒血管超声（DVUS）诊断深静脉血栓形成（DVT）的价值,计算间接CTV的敏感性、特异性、阴性预测值和阳性预测值。结果87例患者中,MSCTPA扫描肺血栓栓塞症（PTE）和DVT均显示32例,显示DVT未显示VIE8例,显示PTE未显示DVT22例。DVUS检查中,DVT42例。与DVUS相比,下肢间接CTV诊断DVT的敏感性95．5％、特异性99．2％、阳性预测值97．7％、阴性预测值98．5％。结论联合应用MSCTPA和间接CTV实现了一次检查同时诊断VIE和DVT,并能显示胸部和下肢的其他异常。     

Deep vein thrombosis: scintigraphic diagnosis with In-111-labeled monoclonal antifibrin antibodies

Fifty-two patients suspected of having deep vein thrombosis under-went scintigraphy with an indium-111-labeled monoclonal antifibrin antibody. Venography disclosed deep vein thrombosis in 31 patients. With the whole limb considered an anatomic entity, antifibrin antibody scintigrams obtained 2 hours after injection had a specificity and sensitivity of 81% and 84%, respectively. A higher sensitivity (92%) was found for a subgroup of patients (n = 44) with symptoms for less than 10 days. Regional sensitivities for all patients and for the subgroup, respectively, were 92% and 100% in the calf, 82% and 94% in the popliteal region, 63% and 71% in the thigh, and only 18% and 13% in the pelvis. Additional imaging performed 6 hours and 21 hours after injection in 12 patients and quantitative analysis done from scintigrams with and without blood-pool (technetium-99m human serum albumin) correction did not improve sensitivity. In-111-antifibrin antibody scintigraphy is an accurate method for diagnosis of acute established deep vein thrombosis of the calf and popliteal region; its sensitivity in the thigh is lower, and it is not feasible for diagnosis in the pelvic area.     

Contrast venography: from gold standard to 'golden backup' in clinically suspected deep vein thrombosis

In a series of 180 patients, clinically suspected of having deep venous thrombosis (DVT), contrast venography was compared with radionuclide phlebography, duplex ultrasonography and strain gauge plethysmography. In most patients lung scintigraphy was also performed to detect pulmonary embolism (PE). Venography was performed on a routine basis. All venograms were read by at least two observers (radiologists or radiologist/resident) and an inter-observer agreement was reached of 96% with a kappa value of 0.935. In six patients venography was technically impossible or inadequate, 58% of the patients actually had DVT and 26% developed pulmonary embolism (PE). Of the patients with proven DVT, 43% developed PE. Of the three other methods duplex scanning scored the best for the detection of proximal thrombosis, with 92%, 90% and 9.2, and strain gauge plethysmography the worst, with values of 72%, 78% and 3.2 for, respectively, sensitivity, specificity and positive likelihood ratio's. On the basis of the presented material and the current literature it is concluded that the choice for a screening test for proximal thrombosis could best be made on the basis of (local) availability, cost-effectiveness and patient comfort. Duplex ultra-sonography is tipped as the most promising method, accepting that distal thrombosis (calf veins) does not play an important role in PE. Contrast venography should be used as a 'golden backup' in any case of doubt.     

Indium-111 chloride imaging with ununited fractures

Twenty patients with ununited fractures and a suspicion of infection had In-111 chloride imaging. Surgically obtained cultures were positive for infection in 12 and negative in eight patients. In-111 chloride images were positive in all 12 patients with infection but also were positive in six of the patients with negative cultures. It is not possible to differentiate infected from noninfected ununited fractures by In-111 chloride imaging.     

Radiolabeled antifibrin antibody in the detection of venous thrombosis: preliminary results

The recent development of monoclonal antibodies against components of coagulated blood may provide new approaches to the diagnosis of venous thrombosis. Scanning with an indium-111-labeled Fab fragment of a murine monoclonal antifibrin antibody (59D8) and ascending contrast venography were performed in 33 patients. Images of the calves, popliteal fossae, thighs, and pelvis were obtained immediately, 4-6 hours, and 24 hours after injection of 2 mCi (74 MBq) of the antibody. All images were read in a blinded manner. Findings in both studies were positive in 28 patients and negative in three. In 19 patients not undergoing heparin therapy, 19 specific anatomic sites were positive on venograms and 29 were positive on antibody images (19 sites matched). In 14 patients undergoing heparin therapy, 34 sites were positive on venograms and 27 were positive on antibody images (22 sites matched). In most patients, positive results were noted within 1 hour of antibody injection. No adverse effects were noted with the antibody preparation. Preliminary data suggest that antifibrin antibody imaging is sensitive in detecting clots, is safe to use, and may have a role in diagnosing and managing venous thrombosis.     

Deep venous thrombosis: detection by using indirect CT venography. The Pulmonary Angiography-Indirect CT Venography Cooperative Group

PURPOSE: To assess the clinical benefits of performing indirect computed tomographic (CT) venography after pulmonary CT angiography to detect deep venous thrombosis (DVT) in patients suspected of having a pulmonary embolism. MATERIALS AND METHODS: The authors prospectively enrolled 541 consecutive patients who underwent pulmonary CT angiography for suspected pulmonary embolism at seven institutions. Using a protocol that optimizes venous enhancement without additional contrast material injection, the authors obtained contiguous images from the pelvis to the popliteal fossa. Ultrasonography (US) also was performed in 116 patients. RESULTS: DVT was found at indirect CT venography in 45 (8%), and pulmonary embolism was found at pulmonary CT angiography in 91 (17%) of 541 patients. Among the 45 patients with DVT, DVT occurred in 16 patients who had no pulmonary embolism at pulmonary CT angiography, which increased the diagnosis of thromboembolic disease by 18%. Among 116 patients who underwent US and indirect CT venography, 15 had DVT at US, and in all 15, DVT also was seen at indirect CT venography. In four additional cases, DVT was seen at only indirect CT venography. CONCLUSION: Among patients suspected to have pulmonary embolism, a substantial number had DVT in the absence of pulmonary embolism. Combined pulmonary CT angiography-indirect CT venography can depict these cases with accuracy comparable to that of US and thus could have a significant effect on patient care.     

Deep vein thrombosis: significant limitations of noninvasive tests

Impedance plethysmography (IPG) has a reputed sensitivity of 95% in the detection of proximal, clinically significant deep venous thrombosis (DVT). A review of the radiologic studies of 100 consecutive patients who underwent both venography and IPG showed venographic evidence of proximal DVT in 40 patients. The IPG was negative in 15 (38%) of these 40 cases. The specificity of the IPG was 83%. The predictive value of a negative study, with this 40% prevalence of DVT, was 77%. These disturbing results indicate a continuing role for venography in the workup of DVT.     

平衡法核素显像诊断下肢深静脉血栓

目的：建立诊断下肢深静脉血栓的平衡期核素检查方法。方法：上肢静脉给药，体内法９９ｍＴｃ标记ＲＢＣ，３０分钟后先做平衡期静脉显像，然后用放射性核素体积描记术（ＲＰＧ）做血流测量。获得双下肢深静脉影像、ＲＰＧ曲线、深静脉回流血量和回流速度。结果：３５０例病人接受检查，其中回流正常者７８例，单侧梗阻１３３例，双侧病变１０８例，深静脉功能不全３１例。５０例病人同时做核素深静脉显像（ＲＮＶ），１０例同时做Ｘ线静脉造影，结果与核素平衡法的符合率均为９０％。结论：核素平衡法可用于临床常规检查，并可取代ＲＮＶ。     

In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients.     

Diagnosis of deep venous thrombosis of the legs: accuracy of ultrasonography using vein compression

We prospectively compared real-time US findings with venographic results in the legs of 171 consecutive outpatients with clinically suspected deep venous thrombosis (DVT). In each leg the common femoral and the popliteal veins were evaluated with venography and US. The two examinations were independently performed and reviewed. Vein compressibility (VC), intraluminal echogenicity and response to Valsalva maneuver were evaluated with US. Venography detected DVT in 54/171 legs. 10/54 legs had isolated distal DVT. With VC, US was 100% specific, 87% sensitive and 96% accurate. 6/7 false negative US studies were due to isolated distal DVT; therefore US sensitivity for proximal DVT was 98%. The other two US diagnostic criteria were much less accurate than VC. VC-US is an accurate, cheap and reproducible test for the detection of DVT in symptomatic outpatients.     

Optimal imaging time for delayed images in the diagnosis of abnormal parathyroid tissue with Tc-99m sestamibi.

PURPOSE: Double-phase scintigraphy with Tc-99m sestamibi is a good method to detect hyperfunctioning parathyroid glands. This study tried to determine the best time for delayed images: 2 or 4 hours. METHODS: Fifty-six patients were studied, and 35 of them had primary hyperparathyroidism (mean age, 53 +/- 13 years; 54% were women). Cervical ultrasonography was performed on 29 of 56 (52%) patients and surgery in 16 of 56 (29%) patients. The dose was 740 MBq (20 mCi) given intravenously, and the acquisition was performed at 10 minutes, 2 h, and 4 h using anterior views, including the mediastinum. Studies that had positive results were analyzed blindly by two independent observers, who selected the best definition for abnormal activity. RESULTS: Nineteen of 56 (34%) studies were negative and 37 of 56 (66%) were positive, 25 of them with one focus and 12 with two or more parathyroid foci. Analysis revealed 76% agreement between the observers (the rest was classified by consensus). In 70% of the cases, the best delayed image was obtained at 2 hours, in 16% at 4 hours (P < 0.00001), and in 14% both images were similar. In those cases with better images at 4 hours, the 2-hour images also showed the lesions. In two patients, lesions were seen only at 2 hours. These results could be explained by tracer decay, washout of parathyroid activity, or both. CONCLUSIONS: The best protocol should include the early 10-minute image and the 2-hour delayed view. Further controls do not appear necessary. This may be important for patient throughput.