Gene therapy for myocardial angiogenesis: initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia.

BACKGROUND: We initiated a phase 1 clinical study to determine the safety and bioactivity of direct myocardial gene transfer of vascular endothelial growth factor (VEGF) as sole therapy for patients with symptomatic myocardial ischemia. METHODS AND RESULTS: VEGF gene transfer (GTx) was performed in 5 patients (all male, ages 53 to 71) who had failed conventional therapy; these men had angina (determined by angiographically documented coronary artery disease). Naked plasmid DNA encoding VEGF (phVEGF165) was injected directly into the ischemic myocardium via a mini left anterior thoracotomy. Injections caused no changes in heart rate (pre-GTx=75+/-15/min versus post-GTx=80+/-16/min, P=NS), systolic BP (114+/-7 versus 118+/-7 mm Hg, P=NS), or diastolic BP (57+/-2 versus 59+/-2 mm Hg, P=NS). Ventricular arrhythmias were limited to single unifocal premature beats at the moment of injection. Serial ECGs showed no evidence of new myocardial infarction in any patient. Intraoperative blood loss was 0 to 50 cm3, and total chest tube drainage was 110 to 395 cm3. Postoperative cardiac output fell transiently but increased within 24 hours (preanesthesia=4.8+/-0.4 versus postanesthesia=4.1+/-0.3 versus 24 hours postoperative=6. 3+/-0.8, P=0.02). Time to extubation after closure was 18.4+/-1.4 minutes; average postoperative hospital stay was 3.8 days. All patients had significant reduction in angina (nitroglycerin [NTG] use=53.9+/-10.0/wk pre-GTx versus 9.8+/-6.9/wk post-GTx, P<0.03). Postoperative left ventricular ejection fraction (LVEF) was either unchanged (n=3) or improved (n=2, mean increase in LVEF=5%). Objective evidence of reduced ischemia was documented using dobutamine single photon emission computed tomography (SPECT)-sestamibi imaging in all patients. Coronary angiography showed improved Rentrop score in 5 of 5 patients. CONCLUSIONS: This initial experience with naked gene transfer as sole therapy for myocardial ischemia suggests that direct myocardial injection of naked plasmid DNA, via a minimally invasive chest wall incision, is safe and may lead to reduced symptoms and improved myocardial perfusion in selected patients with chronic myocardial ischemia.

Radiocolloid liver scintigraphy. A choice and an echo.

A binary classification was used to evaluate the relative usefulness and accuracy of liver imaging with radiocolloid scintigraphy, ultrasonography, and transmission computed tomography. No single technique was found to be significantly superior to the others on the basis of their sensitivity, specificity, and predictive value.

Thyroid scintigraphy: pinhole images versus rectilinear scans.

99mTc-pertechnetate thyroid scintigraphy was performed on 67 patients with a pinhole camera and a rectilinear scanner. The dual set of images was interpreted blindly by four nuclear medicine physicians. Observer performance with each of the two imaging techniques was evaluated by the receiver operating characteristic (ROC) method and by multivariate information analysis (MIA). Performance was superior for the four observers when interpreting the pinhole images, identification accuracy ranging from 70 to 94% with the pinhole images and only 49 to 63% with the rectilinear scanner.

Field flood uniformity correction: benefits or pitfalls?

Strict quality control of scintillation camera images is increasingly recognized as important in a nuclear medicine laboratory. The field flood uniformity of the camera should be tested daily. A variety of commercially available data systems facilitate the above task. Concomitantly, scintigrams are increasingly being corrected for uniformity, namely, unbalanced photo-multiplier tubes, uniformity correction can occasionally, depending on the scatter fraction, produce clinically significant artifacts. This effect is due to the application of a linear correction factor to a nonlinear phenomenon.

Cesium-129 myocardial scintigraphy to quantify myocardial infarction in dogs.

The sizes of surgically induced acute myocardial infarctions were quantified in a study of 28 dogs. Four projections (right and left anterior oblique, anterior, and left lateral) were obtained with 129Cs myocardial scintigraphy. Control images, taken before surgery, were compared with images taken 24-72 hr after coronary artery ligation. From postmortem examination the size of the infarct was determined and expressed as a percentage of the total left ventricle. On a standard diagram four independent observers marked the infarcted areas in each projection, expressed the severity of involvement in each area, and determined overall infarction size as a percentage of the total left ventricle. A nonlinear least-squares method was also employed to derive the size of the infarct, using the results from each observer's diagram. There were positive correlations between each observer's percentage estimate and the autopsy results. The overall accuracy of the least-squares method was similar to that of the individual observers. In this study, Observer 3 proved that acute myocardial infarcts can be quantified accurately from multiple scintigraphic projections of the myocardium, but the other three observers had difficulty in estimating infarct size. This difficulty probably resulted from the lack of well-validated criteria to aid the observer in determining the area of infarction, the severity of involvement within that area, or the total size of a myocardial infarct. Improvement in these estimates will require the development of definitive criteria, the use of optical scanners or computer processing, and combinations of radionuclides.

Quantitative assessment of field uniformity for gamma cameras.

Objective criteria for judging the uniformity of field floods are developed and the effects of the energy window and scatter material on uniformity are examined. There is a highly significant correlation (p = 0.99) between a 14% difference in average count among adjacent photomultiplier tube regions and observer detection of detuned areas. Similarly, a 10% average count difference is not significantly recognized as a nonuniform area. Results indicate that there is a complex interaction between uniformity, energy window (15-30% symmetrical) and 0-7.6 cm of tissue-equivalent scatter medium interposed between the flood source and the collimator. Quantitation of the flood should be performed to indicate which regions need retuning.

The Gamut approach to scintigram interpretation--diagnostic aid and teaching method.

A Gamut is defined as a complete list of anything. As utilized here, it indicates a complete list of the possible causes of a particular scintigram finding. The procedure for developing a Gamut is discussed, ant its use as a tool for instructing residents in nuclear medicine is described. Sample Gamuts are presented and the Gamut approach to scintigram differential diagnosis is described.

Hepatic artery traumatic aneurysm.

The diagnosis of intrahepatic aneurysm was suspected following radioisotope scintigraphic studies. A patient developed abdominal pain following blunt abdominal trauma. The scintigrams of the liver revealed a large intrahepatic defect and separation between lung and liver. Angiogram revealed a large false aneurysm of the right hepatic artery.

Interpretation of radionuclide liver images: do training and experience make a difference?

Individual observers interpreted images in order to assess their accuracy and sources of error. Seventy-six liver images were presented to nine readers for interpretation. Readers of differing experience participated in the study: four radiology residents, three fellows in nuclear medicine, and two full-time nuclear medicine physicians. A higher incidence of false-positive reading was more common in inexperienced observers (11-50%) and the most correct readings were obtained by staff physicians (88% overall percentage accuracy). Heterogeneity in radionuclide uptake was the most frequently ill-defined nature was the most common false-positive finding in normal cases. Early stages of cirrhosis, mild hepatitis, and rare diseases such as hepatic sarcoidosis were difficult to detect. Skill of interpretation improved with experience, especially in judging heterogeneity of an ill-defined nature, and the rate of accurate readings was proportional to the level of training of the observer.