Transmission maximum-likelihood reconstruction with ordered subsets for cone beam CT.

An iterative algorithm is presented for accelerated reconstruction of cone beam transmission CT data (CBCT). CBCT supplies an attenuation map for SPECT attenuation compensation and anatomical correlation. Iterative algorithms are necessary to reduce truncation artifacts and 3D reconstruction artifacts. An existing transmission maximum-likelihood algorithm (TRML) is accurate but the reconstruction time is too long. The new algorithm is a modified EM algorithm, based on ordered subsets (OSEM). OSEM was evaluated in comparison to TRML using a thorax phantom and a 3D Defrise phantom. A wide range of image measures were evaluated, including spatial resolution, noise, log likelihood, region quantification, truncation artifact removal, and 3D artifact removal. For appropriate subset size, OSEM produced essentially the same image as TRML, but required only one-tenth as many iterations. Thus, adequate images were available in two to four iterations (20-30 min on a SPARC 2 workstation). Further, OSEM still approximately maximizes likelihood: divergence occurs only for very high (and clinically irrelevant) iterations. Ordered subsets are likely to be useful in other geometries (fan and parallel) and for emission CT as well. Therefore, with ordered subsets, high-quality iterative reconstruction is now available in clinically practical reconstructions times.

The transition from technegas to pertechnegas.

UNLABELLED: We set out to determine the oxygen concentration of the argon-oxygen mixture in the technegas generator where technegas-like behavior changes to pertechnegas-like behavior which allows [99mTc]pertechnetate to enter the solution. METHODS: We prepared radioaerosols analogous to technegas and pertechnegas, with oxygen concentrations between 0% and 5%. They then were examined by thin-layer chromatography using saline as a solvent to measure the amount of [99mTc]pertechnetate moving with the solvent front as a function of oxygen concentration. RESULTS: The amount of mobile pertechnetate markedly increased when the radioaerosols were created in an atmosphere containing between 0.1% and 0.2% oxygen. The transition from technegas-like to pertechnegas-like behavior occurs when the oxygen-argon gas mixture contains lower concentrations of oxygen than those used in the preparation of pertechnegas. CONCLUSION: Argon intended for the preparation of technegas should contain no more than 0.1% oxygen.

Characterization of tumor-infiltrating lymphocytes from murine mammary adenocarcinomas.

The aim of this investigation was to assess the in vitro functional and phenotypic characteristics of lymphocytes isolated from C3H mouse mammary adenocarcinomas. A protocol was developed for the expansion of TILs in long-term culture. The homing pattern of TILs prepared and grown in this manner was studied. Cells that had been in culture for up to 96 days accumulated at higher levels in mammary tumors than in corresponding normal mammary tissue 24 hr after adoptive transfer. The ability of cultured TILs to lyse YAC-1 cells was determined. Peak activity was demonstrated by lymphocytes that had been in culture for three days. By two weeks in culture the level of cytotoxicity returned to that of fresh TILs, and after 45 days it was negligible. T cells were the major constituents in all preparations. The relative frequency of CD8+ cells remained fairly constant over time in culture, but that of CD4+ cells declined. At all time points the CD4:CD8 ratio for TILs was less than 1. The percentage of ASGM1+ bright cells among fresh TILs was low. It increased dramatically within 3 days, remained high for about 7 weeks, and then declined rapidly to pre-culture levels. An unusual large cell characterized by the presence of an intensely PAS positive peripheral region was observed.

Phantom study of breast tissue attenuation in myocardial imaging.

The attenuation of photons by the breasts and other soft tissue overlying the chest may decrease the diagnostic accuracy of SPECT myocardial imaging. In this experiment, we measured the attenuation distortion of myocardial polar maps using a thorax phantom with a cardiac insert and added breast tissue. The distortion was measured using a regional semiquantitative analysis. Attenuation compensation was performed using a conebeam radionuclide CT attenuation map. Breast tissue attenuation created apparent "defects" in the polar map, where the intensity was reduced by up to 35% relative to the most intense region. However, the size, location and severity of the reduction depended on cardiac insert orientation and breast placement. For the geometries studied, apparent "defects" were observed in the anterior wall, the apex, the inferior wall and basal regions. These results suggest that attenuation artifacts may occur in almost any location. However, the attenuation compensation nearly eliminated the apparent defects and improved polar map symmetry. After compensation, the variations between regions were generally 5% or less. Therefore, we expect that attenuation compensation will improve diagnostic accuracy in myocardial imaging in female patients and in males with excessive musculature or soft tissue. Without such compensation, diagnosis may be compromised.

Experimentally produced pulmonary arterial occlusion in the dog: identification with pertechnegas inhalation.

Pertechnegas, a variant of technegas, is a fine, dry aerosol formed when technetium-99m pertechnetate is vaporized in a technegas generator under appropriate conditions. After inhalation, the aerosol is deposited almost entirely on the surfaces of terminal respiratory structures. Unlike technegas, however, pertechnegas crosses the alveolar-capillary membrane and leaves the lung through the pulmonary circulation. To demonstrate prolonged retention of pertechnegas in regions of lung supplied by an occluded pulmonary artery, 12 pulmonary arterial occlusions were experimentally produced in two dogs. After inhalation of pertechnegas, a transient focus of increased pulmonary radioactivity was seen in 11 occlusions; 10 of these 11 foci were easily confirmed by means of subsequent perfusion scintigraphy. All 11 foci of retained pertechnegas corresponded to the location of the non-perfused lung. Thus, it is possible to identify ischemic lung with focal retention of pertechnegas (a finding that indicates preserved ventilation but diminished perfusion) by use of a single examination.

Thrombus imaging: a comparison of radiolabeled GC4 and T2G1s fibrin-specific monoclonal antibodies.

Radioimmunoimaging of experimentally-induced canine thrombi has previously been achieved with iodine-131- and indium-111-labeled (131I and 111In) anti-fibrin T2G1s monoclonal antibody (MAb). We now compare T2G1s to another anti-fibrin MAb, designated GC4, for imaging fresh and aged canine thrombi. GC4 is specific for a neoepitope exposed on fibrin later in the thrombolytic process after plasmin digestion. Femoral venous thrombi were induced in six groups of dogs, each containing three dogs. In two groups, the MAbs were compared when the thrombi were 3-hr or 3-days old at the time of injection, and the dogs were killed at 48 hr. In thrombi 3-hr-old, the GC4/T2G1s concentration ratio averaged 0.53 compared to 1.9 in 3-day-old thrombi. Two groups of dogs with thrombi 1- or 3-days-old were heparinized before MAb injection and were killed at 24 hr. The heparinized dogs with thrombi 1- or 3-days-old had GC4/T2G1s mean ratios of 2.3 and 2.9, respectively. In the unheparinized groups, the corresponding ratios were 1.1 and 1.9. GC4 may be more useful for clinical thrombus imaging than T2G1s because spontaneous venous thrombi are usually several days old at the time of presentation and patients are often heparinized immediately.

Preferential homing of tumor-infiltrating lymphocytes in tumor-bearing mice.

In view of the current interest in the use of lymphoid cells in adoptive immunotherapy of patients with advanced cancer, we have studied the homing patterns of various lymphoid effector cells in mammary-tumor-bearing mice. Single-cell suspensions of total splenocytes, natural killer (NK) cells, and lymphokine-activated killer (LAK) cells were prepared from the spleens of C3H/OuJ mice. Tumor-infiltrating lymphocytes (TIL) were isolated from mammary adenocarcinomas excised from retired breeder females of the same substrain. Effector cells were labeled with indium-111 and injected via a tail vein into female C3H/OuJ mice bearing one or more mammary tumors. Twenty-four hours after administration, total splenocytes, NK cells, and LAK cells distributed themselves evenly between normal mammary tissue and mammary adenocarcinomas. Only TIL had a higher concentration in tumors than in corresponding normal mammary tissue. The ability of the different lymphocyte preparations to lyse YAC-1 cells was determined by means of a 4-h 51Cr-release cytotoxicity assay. Cells harvested from LAK cell cultures and further enriched by centrifugation through a discontinuous Percoll gradient and interleukin-2 (IL-2)-stimulated TIL demonstrated the highest levels of cytotoxicity, while total splenocytes and fresh TIL were characterized by the lowest levels. Since IL-2-stimulated TIL were highly cytotoxic and exhibited better tumor localization than both NK cells and LAK cells in this system, they may be the lymphoid effectors of choice for adoptive immunotherapy of advanced cancer.

Migratory patterns of different indium-111 labeled leukocyte populations (chiefly lymphocytes) from control and thymectomized rats.

The blood clearance and 24-hr organ distribution of five lymphocyte-rich suspensions harvested from different source organs were compared in the Wistar rat, after labeling with [111In]tropolone and intravenous injection. Peripheral blood lymphocytes (chiefly T cells) had the highest levels in the blood and lymph nodes, a relatively higher level in intestine and a lower level in the spleen than other suspensions. Thymocytes cleared promptly from the blood, accumulated markedly in the liver, moderately in the spleen, but very poorly in other organs, including the thymus. Splenic cells (rich in B cells) sequestered predominantly in the spleen and liver. Splenic cells nonadherent to nylon wool (T-cell enriched) had a relatively high uptake in lymph nodes and marrow. Splenic cells from thymectomized rats (NK cell enriched) localized predominantly in the liver and spleen, and poorly in lymph nodes. We conclude that the source organ for harvesting rat lymphocytes is an important determinant in their localization, as well as other factors such as the techniques of isolation, the toxicity and stability of the radioactive label and the cell radiation dose from internalized radioactivity.

Airflow patterns in a human nasal model.

Nasal airflow patterns were studied by using xenon 133 gas to image the course taken by air as it flowed through a plastic model of the human nasal cavity. The model was produced from the head of a human cadaver, and was anatomically correct. A needle catheter was used to infuse the radioactive xenon into a continuous flow of room air maintained through the model by a variable vacuum source connected to the nasopharynx. The radioactive gas was infused at one of five release sites in the nostril, and the distribution of the radioactivity was imaged in the sagittal plane with a scintillation camera. The data were organized to show the activity in six contiguous regions of the midnose. For each catheter, release site activity patterns were determined for three flow rates. The results of this experiment showed that both catheter position and flow rate had significant and reproducible effects on the distribution of radioactivity within the model.

Detection of experimentally produced acute pulmonary arterial occlusion by methyl iodide-131 inhalation imaging.

Methyl iodide-131 (CH3I-131) is described as an agent for detection of acute experimentally produced pulmonary arterial occlusion in dogs. When gaseous CH3I-131 is inhaled, radioactivity passes instantaneously from the alveoli to the lung capillary bed. Where pulmonary blood flow exists, activity is washed out into the systemic circulation, but in areas of blood stasis, a transient pulmonary "hot spot" remains. CH3I-131 is easily produced and inexpensive, but administration is awkward and strict radiation safety precautions are mandatory.

Distribution of leukocytes labeled with In-111 oxine in dogs with acute inflammatory lesions.

The biodistributions of In-111 oxine (with and without leukocyte labeling) of Ga-67 citrate and of In-111 chloride were compared in 30 dogs with chemical and bacterial abscesses and acute joint inflammation. Serial blood samples were taken and tissues radioassayed at 24 hr. The concentration of In-111-oxine leukocytes in all three types of inflammatory lesion was invariably much higher than that of Ga-67 injected simultaneously. For bacterial abscesses, the mean abscess-to-muscle concentration ratio was 3,000 for labeled leukocytes and 72 for Ga-67. Aqueous buffered In-111 oxine sulfate solution appeared better for labeling leukocytes than In-111 oxine in ethanol. When In-111 oxine was not incubated with leukocytes before injection, or if the cells were poorly labeled or damaged, the abscess localization was often inferior to that of gallium. Localization of In-111 chloride also appeared inferior to that of gallium. No significant difference in distribution in the major organs or inflammatory lesions was demonstrable between labeled suspensions of "pure"neutrophils harvested by elutriation and "mixed"cell suspensions of leukocytes after erythrocyte sedimentation with hydroxyethyl starch. For both types of leukocyte suspension labeled with In-111 oxine, the average recovery of cell-bound activity in the circulating blood at 4 hr was 32% of the administered activity, inferior to that of DFP-32. It is concluded, therefore, that In-111 oxine is a more effective agent than Ga-67 for the detection of acute focal inflammatory lesions if leukocytes are properly labeled, but current techniques are unsatisfactory for the study of neutrophil kinetics.

Experimental and clinical trials of new 99mTc-labeled hepatobiliary agents.

Several new derivatives of lidocaine were synthesized and used to examine the intra- and extrahepatic bile ducts and gallbladder. Diisopropyl-IDA exhibited approximately twice the bile concentration of 131I-rose bengal during the first hour after injection. P-butyl-IDA also concentrates moderately well in the bile and has the added advantage of very low excretion into the urine (2%). It seems more effective than the other IDA derivatives at high bilirubin levels.

An evaluation of 99mTc-labeled hepatobiliary agents.

Scintigraphic imaging of the hepatobiliary system has been significantly improved with the development of 99mTc-labeled compounds. Two of the most promising agents, pyridoxylideneglutamate and HIDA, each formed the basis for the development of a group of structural analogs. Condensation of pyridoxal with leucine and arginine (in place of glutamate) produced pyridoxylideneleucine and pyridoxylidenearginine. Since increasing the molecular weight and the lipid solubility of compounds tends to enhance their biliary excretion, several new IDA derivatives were synthesized by altering the lipophilic substituents on the ring of HIDA. The substitutions included ethyl and ethoxy groups as well as iodine. All compounds were compared with 131I-rose bengal using a baboon model that allowed blood, bile, and urine collection.