Nuclide Imaging To Detect The Pulmonary Artery/lower Limb Venous Thrombosis Experiment And Clinical Research And Diagnosis Of Pulmonary Embolism

Objective:The objective of this study was to explore the impact of P4-DMP444and DMP444on biological properties (biodistribution, excretion kinetics, and capability to image thrombi) of99mTc radiltractive using canine Deep vein thrombosis and pulmonary embolism models imaging studies with/without the heparin heparin pretreatment. Theses studies were specifically designed to explore the impact of heparin treatment on thrombosis uptake of99mTc-P4-DMP444.Methods:Biodistributiong studies were performed using Sprague-Dawley (SD) rats.16SD rats were sacrificed by sodium pentobarbital overdoes (200mg/kg) at5,30,60, and120min postinjection (p.i.). Blood samples were withsdrawn from the heart and rats. The brain eyes heart, spleen, lungs liver, kidneys, muscle, and intestine were harvested, washed with saline, dried, weighed, and calculated the organ uptake as the percentage of injected dose per gram of organ mass (%ID/g). The experimental PE and DVT were induced in5dogs.2mL samples of venous blood was collected at30s,2min,3min,4min,5min,10min,15min,30min,60min,90min and120min respectively after injection. The collected blood samples were weighed and counted for radioactivity in a gamma-counter. The radioactivity is expressed as a percentage of the initial (30s) activity and the blood clearance rate at each time point were obtained. The images of lungs and legs were acquired at15min,30min,60min,90min and120min after injection. Regions-of-interest (ROIs) were drawn on PE, DVT, lung, and leg muscle for determination of PE/lung and DVT/muscle. PE and DVT were removed, weighed and counted for radioactivity ex vivo to determine%ID/g. Changes between the means within a group at different time points were assessed with one-way repeated-measures ANOVA test.Comparision between two radiotracers was made with two-way ANOVA test.Results:It was found that replacing the CA linker with PEG4could enhance the radiotracer clearance kinetics from blood and normal organs in both rats and dogs. The fact that99mTc-P4-DMP444and99mTc-DMP444share very similar thrombosis uptake in both DVT and PE models suggests that the PEG4linker has little effect on GP II b/IIIa binding affinity of cyclic RGD peptide. Even though99mTc-P4-DMP444had less accumulation than99mTc-DMP444in the blood, heart lungs, and muscle over the2h study period in both rats and dogs the difference in PE/lung and DVT/muscle ratios is marginal, suggesting that one PEG4linker is not sufficient to dramatically change the contrast between thrombus and background. It is very important to note that the heparin treatment of dogs with DVT and PE resulted in dramatic decrease in accumulation of99mTc-P4-DMP444in fresh thrombi.Conclusion:On the basis of these results, we believe that99mTc-DMP444and99mTc-P4-DMP444are excellent radiotracers forimaging both DVT and PE, and should be used in patients without antithrombosis treatment at the time of imaging. Objective:Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the most common cause of sever pulmonary hypertension. Timely diagnosis of CTEPH could help to improve the prognosis of patients. The aim of this study was to compare the diagnostic efficacy of V/Q and that of CTPA for CTEPH.Methods:133consecutive patients (54male.79female, aged43.1±14.9years) suspected of having CTEPH were prospectively enrolled in the study. All patients were performed V/Q scintigraphy, CTPA and pulmonary angiography within7days of clinical presentation. Pulmonary angiography is considered the gold standard. Diagnosis of V/Q scan included CTEPH high probability, intermediate probability and low probability; results of CTPA included CTEPH present (one or more pulmonary artery filling defect), CTEPH absent (no filling defect in the pulmonary artery) or non-diagnostic (can not determine pulmonary embolism positive or negative). Kappa test was used to analyze the degree of agreement between the image modalities. The differences between the image modalities were tested for significance using nonparametric and parametric chi-square test where appropriate.Results:All133patients by right heart catheterization confirmed the existence of pulmonary hypertension (mPAP>25mmHg).51patients (38.3%) had a final diagnosis of CTEPH. The other82patients were respectively diagnosed as idiopathic pulmonary arterial hypertension (n=60), Takayasu’s arteritis (n=19) and atrial septal defect (n=3). The sensitivity, specificity, accuracy, PPV and NPV of V/Q scan with high probability as CTEPH positive were96.1%(49/51),75.6%(62/82),83.5%(111/133),71.0%(49/69),96.9%(62/64). The sensitivity, specificity, accuracy, PPV and NPV of V/Q scan with high probability and intermediate probability as CTEPH positive were100%(51/51),73.2%(60/82),83.5%(111/133),69.9%(51/73).100%(60/60). CTPA showed92.2% (47/51) sensitivity,92.7%(76/82) specificity,92.5%(123/133) accuracy,88.7%(47/53) PPV and95.0%(76/80) NPV. When high probability V/Q scanning findings were considered as positive, the agreement between V/Q scan and CTPA was80.5%(107/133)(Kappa=0.612, P<0.001). When high probability and intermediate probability V/Q scanning findings were considered as positive, the agreement between V/Q scan and CTPA was80.5%(107/133)(Kappa=0.677, P<0.001).Conclusion:V/Q scan has a ideal sensitivity for diagnosis of CTEPH. CTPA has higher ability to identify different pulmonary hypertension especially Takayasu’s arteritis. Combination of the two methods may help to further improve the diagnostic accuracy of CTEPH. Objective:To evaluate diagnostic value of the The Prospective Investigative Study of Acute Pulmonary Embolism (PE) Diagnosis (PISA-PED) and Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED II) criteria for lung scintigraphy and compare it with CT pulmonary angiography (CTPA) for the detection of pulmonary embolism (PE).Methods:Five hundred and forty-four consecutive patients with suspected PE were enrolled. All patients underwent lung ventilation/perfusion (V/P) scan, chest radiography, and CTPA. The interval between CTPA and V/Q scan ranged from1to3days. Pulmonary contrast angiography was performed in patients in whom pulmonary embolism was not conclusively diagnosis or ruled out by the noninvasive test. Two readers used the PIOPED II criteria, and2used the PISA-PED criteria for the interpretation of lung scintigraphy. CTPA scans were interpreted by2experienced radiologists. Lung scintigraphy and CTPA were categorized as PE present, absent or non-diagnostic. The final diagnosis was made at a consensus meeting using a composite reference test while taking into account clinical data, all available laboratory recorders, all imaging modalities, the opinions of the physicians responsible for treatment, and clinical follow-up of at last six months. Kappa test was used to analyze the degree of agreement between the image modalities. The differences between the image modalities were tested for significance using chi-square test.Results:PE was present in321of544patients. Wells test showed that218(218/544,40.1%) patients had low probability of PE (Wells score<2), and236(236/544,43.4%) patients had intermediate probability of PE (Wells score=2-6), and90(90/544,16.5%) patients had high probability of PE (Wells score>6). Using PIOPED Ⅱ criteria, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were85.1%,82.5%,88.1%, and78.4%respectively for V/P scan. Using PISA-PED criteria, sensitivity, specificity, PPV, and NPV were86.0%,81.2%,86.8%, and80.1% respectively, and none was non-diagnostic. Sensitivity, specificity, PPV, and NPV were81.7%,93.4%,94.9%, and77.3%respectively for CTPA. Proportion of non-diagnostic results on the PIOPED Ⅱ interpretation and CTPA is significant, but there was no non-diagnostic result on the PISA-PED interpretation (p<0.05). After excluding the non-diagnostic results, the agreement was good between the PIOPED Ⅱ and the PISA-PED interpretation (Kappa value=0.97), and moderate between the PIOPED Ⅱ interpretation and CTPA (Kappa value=0.59), and between the PISA-PED interpretation and CTPA (Kappa value=0.58).Conclusions:PISA-PED interpretation has similar diagnostic accuracy to PIOPED Ⅱ interpretation, does not have non-diagnostic scan, with lower cost and radiation, thus should be considered as a first choice for patients with suspected PE. Objective:The aim of this study was to compare the diagnostic efficacy of planar V/Q scintigraphy and single-photon emission computed tomography (SPECT) scintigraphy in diagnosis of plumonary embolism (PE).Methods:114consecutive patients (43male,71female, aged56±16years) suspected of PE (Well’s score≥2or D-dimer≥500μL) were prospectively enrolled in the study. All patients were performed V/Q planar scintigraphy and V/Q SPECT scintigraphy within1day. First was performed planar imaging of lung ventilation, and pulmonary ventilation SPECT imaging, followed by lung perfusion SPECT imaging and planar imaging of lung perfusion. V/Q planar imaging interpretation based on modified prospective investigation of pulmonary embolism diagnosis Ⅱ (PIOPEDⅡ). Diagnosis of V/Q planar scan included PE positive, PE negative and non-diagnostic. V/Q SPECT imaging interpretation according to the recommended criteria for reading V/PSPECT with respect to acute PE described in the European Guidelines. Diagnosis of V/Q SPECT scan included PE positive, PE negative and non-diagnostic. The final diagnosis was made at a consensus meeting using a composite reference test while taking into account clinical data, all available laboratory recorders, all imaging modalities, the opinions of the physicians responsible for treatment, and clinical follow-up of at last six months. Kappa test was used to analyze the degree of agreement between the image modalities. The differences between the image modalities were tested for significance using chi-square test.Results:Of all114patients,63patients (55.3%) had a final diagnosis of PE. The other51patients (44.7%) were excluded PE. V/Q planar imaging indicated PE positive in48cases, negative in63cases, non-diagnostic in3cases. V/Q SPECT imaging showd PE positive in55cases, negative in58cases, non-diagnostic in1cases. Excluded3non-diagnostic results, the sensitivity was72.6%, specificity was93.9%, accuracy was 82.0%, PPVwas93.8%and NPV was73.0%of V/Q planar scan. Excluded1non-diagnostic results, the sensitivity, specificity, accuracy, PPV, and NPV were respectively81.0%,92.0%,85.8%,92.7%, and79.3%. There were no significant differences between sensitivity, specificity, accuracy, PPV, and NPV of V/Q planar imaging and V/Q SPECT imaging (P>0.05). The results were different between the two methods (χ2=92.6, P<0.001). The agreement between V/Q planar scan and V/Q SPECT scan was high (Kappa=0.91, P<0.001).Conclusion:V/Q SPECT scan can provide similar specificity comparable to V/Q planar scan, but has a ideal sensitivity and accuracy for diagnosis of PE. The detection of segmental PE and especially sub-segmental PE by V/Q SPECT scan was high and non-diagnostic results were less than V/Q planar imaging. V/Q SPECT scintigraphy can instead of planar scan as a radionuclide imaging in the diagnosis of PE.