Tomographic assessment of regional brain perfusion in cerebrovascular disease.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to P Gerundini.
Explore the source record for details and available documents.
The biodistribution of the three cationic 99mTc complexes [99mTc(TMP)6]+, [99mTc(POM-POM)3]+, and [99mTc(TBIN)6]+--where TMP represents trimethylphosphite, POM-POM represents 1,2-bis(dimethyoxyphosphino)ethane, and TBIN represents t-butylisonitrile--have been evaluated in humans and dogs. Each agent was studied in three normal volunteers at rest, while [99mTc(POM-POM)3]+ and [99mTc(TBIN)6]+ were each studied in one normal volunteer at exercise. Even though all three agents yield good myocardial images in dogs, none appear suitable for clinical use as myocardial perfusion imaging radiopharmaceuticals. In humans, [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ clear very slowly from the blood and provide myocardial images only several hours after injection. [99mTc(TBIN)6]+ clears rapidly from the blood, but accumulation in the lung obscures the myocardial image for the first hour after injection; at later times, activity in the liver and spleen masks the apical wall. These results correlate with the blood-binding properties of the three complexes. [99mTc(TMP)6]+ and [99mTc(POM-POM)3]+ bind tightly to the plasma of human blood, but not to the plasma of dog blood; [99mTc(TBIN)6]+ does not bind tightly to the plasma of either dog or human blood. Among the Tc(I) complexes studied to date in humans, [99mTc(TBIN)6]+ appears to be unique in biodistribution pattern, blood-binding properties, and the fact that exercise improves the ultimate myocardial image. All the Tc(I) complexes appear to undergo myocardial accumulation by a mechanism different from that utilized by Tc(III) complexes. Animal studies alone are not adequate to evaluate the potential utility of 99mTc cationic complexes for myocardial perfusion studies.
A limitation of first-pass radionuclide angiocardiography is the limited repeatability because of the relatively long half-life of technetium-99m (Tc-99m). The feasibility, reproducibility and validity of multiple sequential quantitative first-pass studies were assessed in humans using the short-lived isotope gold-195m (Au-195m) (half-life of 30.6 seconds, 262 keV), which can be directly obtained from a generator made of its parent isotope, mercury-195m (half-life of 41.6 hours). Thirty-three subjects (13 normal volunteers and 20 cardiac patients) were studied using a large-field gamma camera equipped with a medium-energy collimator. After Au-195m intravenous injections, repeat first-pass studies were performed in the left anterior oblique projection. A left anterior oblique study was then obtained after i.v. injection of Tc-99m. Left ventricular ejection fraction calculations were performed separately by 2 observers. Reproducibility of Au-195m first-pass studies was excellent. The correlation coefficients for left ventricular ejection fraction from the first and the second Au-195m injections were 0.93 and 0.98 for observers 1 and 2, respectively. The correlation coefficients between Au-195m and Tc-99m first-pass studies were 0.95 and 0.98, respectively.
Technetium-99m labeled bis(1,2-diethylphosphino)ethane was evaluated as a cardiac perfusion agent in mice, dogs and normal human volunteers. The agent produced as a single cationic compound was prepared by a simple kit type method and had a rapid myocardial uptake in animals. The cardiac uptake of the agent in dogs averaged 4.6% of administered dose and delineated left and right ventricles by in vivo imaging. In dogs with experimental myocardial infarction, the agent was distributed according to the regional myocardial blood flow, had excellent correlation with myocardial distribution of 85Sr microspheres (r = 0.96, 0.93)] and 201Tl (r = 0.91 and 0.83), and enabled us to detect perfusion defects by in vivo scintigraphy. The agent, however, failed to have a useful degree of cardiac uptake in humans.
The feasibility of assessing regional cerebral perfusion using the new brain imaging agent N,N,N'-trimethyl-N'-(2)-hydroxy-3-methyl-5-(123I) iodobenzyl)-1,3-propanediamine 2 HCl (I-123 HIPDM) and single photon emission computed tomography (SPECT) was evaluated in normal subjects and patients with cerebrovascular disorders. Following intravenous injection, I-123 HIPDM was rapidly extracted from the circulating blood by the brain (6.7%) and other organs. Its intracerebral distribution, as tomographically assessed by SPECT with a rotating gamma camera, reflected the distribution of blood flow within brain structures (gray and white matter, basal ganglia, etc.). Asymptomatic patients with history of transient ischemic attacks or minor stroke and angiographic evidence of internal carotid artery occlusion showed large cortical areas of reduced I-123 HIPDM distribution with normal or slightly positive CT. After extracranial-intracranial bypass surgery, reperfusion could be shown in previously ischemic areas. This study indicates the clinical usefulness of using I-123 HIPDM and gamma camera SPECT for the functional evaluation of brain disorders.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Serial angioscintigraphy with 99mTc-pertecnetate and gamma camera was carried out in more than 500 cases of cerebropathies with various but prevalently vascular pathogenesis. Pictures are described and discussed with reference to the differential diagnosis, and a number of significant cases are reported in detail.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The deficiency of dystrophin, a sarcolemmal associated protein, is responsible for Duchenne muscular dystrophy (DMD). Gene replacement is attractive as a potential therapy. In this article, we describe a new method for myoblast transplantation and expression of dystrophin in skeletal muscle tissue of dystrophin-deficient mdx mouse through iliac vessels extracorporeal circulation. We evaluated the extracorporeal circulation as an alternative route of delivering myoblasts to the target tissue. Two series of experiments were performed with the extracorporeal circulation. In a first series, L6 rat myoblasts, transfected with LacZ reporter gene, were perfused in limbs of 15 rats. In the second series, the muscle limbs of three 6-8-week-old mdx were perfused with myoblasts of donor C57BL10J mice. Before these perfusions, the right tibialis anterior (TA) muscle of the rats and mdx was injected three times at several sites with bupivacaine (BPVC) and hyaluronidase. The ability of injected cells to migrate in the host tissue was assessed in rats by technetium-99m cell labeling. No radioactivity was detected in the lungs, bowels, and liver of animals treated with extracorporeal circulation. The tissue integration and viability of the myoblasts were ultimately confirmed by genetic and histochemical analysis of LacZ reporter gene. Following a single extracorporeal perfusion of myoblasts from donor C57BL10J, sarcolemmal expression of dystrophin was observed in clusters of myofibers in tibialis anterior muscles previously treated with BPVC and hyaluronidase. Furthermore, large clusters of dystrophin-positive fibers were observed in muscles up to 21 days after repeated treatments. These clusters represented an average of 4.2% of the total muscle fibers. These results demonstrate that the extracorporeal circulation allows selective myoblast-mediated gene transfer to muscles, opening new perspectives in muscular dystrophy gene therapy.
Explore the source record for details and available documents.
Explore the source record for details and available documents.