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[Automated evaluation and analysis of isotopic heart function tests with minimal cardiac transit times].

The clinical evaluation of cardiac function by non-invasive means with the help of radioactive isotopes registering minimal cardiac transit times (MTTs) is increasingly employed in routine diagnosis. In order to economise on work load and time expenditure and for the purpose of an objective and complete evaluation of data, automatic data processing is desirable. This paper describes a program that consists of 4 sections: 1. examination 2. generation of data 3. processing of data 4. evaluation of data. The program permits a nearly total automated data generation, analysis, calculation, classification, final clinical evaluation and the automated production of a medical report. This greatly reduces the time spent per examination to approximately 5 minutes. The automated evaluation of the data is based on clinical experience with approximately 3.500 measurements in patients with the most frequent cardiac diseases. The result is an objective statement of causes of MTT changes and is highly useful for medical routine application. The control and the final inclusion of the findings into the spectrum of other clinical results remains the subject of the physician's judgement. The advantage of the method is the evaluation of all cardiac segments. This pertains to the evaluation of both atria and both ventricles, as well as of the entire central circulation with and without participation of the lung.

Computers↗

Splenic pooling of granulocytes.

The intrasplenic kinetics of granulocytes, isolated in plasma and labelled in plasma with 111In-tropolonate, have been studied in normal subjects, patients with negative studies for inflammatory disease and patients with positive studies, with the aim of identifying the nature of splenic activity seen after 111In-labelled granulocyte administration. Up to 40 min after injection, 111In activity was visible only in major blood vessels, liver and spleen, with slight, abnormal activity visible in most of those with positive scans. The time courses of uptake of hepatic and splenic activity were different, with liver activity rapidly reaching a plateau and splenic activity increasing mono-exponentially to a plateau achieved between 20 and 40 min. The clear difference between the shapes of the hepatic and splenic uptake curves and the magnitude of the splenic uptake rate constant indicated that splenic activity represented reversible uptake. The application of deconvolution analysis to the blood and splenic time-activity curves generated a splenic retention (or washout) curve consistent with dynamic exchange of granulocytes between blood and spleen. The slope of this curve indicated an intrasplenic granulocyte transit time of 9.3 (+/- SE 0.6) min. Taking splenic activity to be reversible, comparison of the 111In signal from the spleen 40 min after injection of 111In-labelled granulocytes with that given from the spleen after the injection of 111In-labelled erythrocytes (relative to their respective blood levels) indicated that intrasplenic granulocyte transit time was 14.4 (+/- SE 1.1) times that of erythrocytes. Based on actual erythrocyte time, this corresponds to a granulocyte transit time of 8.6-11.5 min, in close agreement with the estimate based on deconvolution analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Colitis↗

I-123 metaiodobenzylguanidine cardiac scintigraphy in patients with an implanted permanent pacemaker.

T1 scintigraphic abnormalities have been reported in patients with an implanted permanent pacemaker, but little is known about the MIBG scintigraphic findings in such patients. This study was performed to assess the MIBG scintigraphic findings in patients with an implanted permanent pacemaker, and to test the hypothesis that imaging characteristics of MIBG scintigraphy differ according to its mode. Twelve patients (4 men and 8 women, mean age: 72.4 +/- 9.5 years), who had undergone the implantation of a permanent pacemaker for bradyarrhythmias, underwent MIBG scintigraphy. The patients were divided into VVI pacemaker and DDD pacemaker groups. The tomograms were divided into nine segments and the MIBG defect in each segment scored on a scale ranging from 0 (normal uptake) to 3 (no uptake). Total MIBG defect scores were generated by summing the scores for the nine segments in each patient. MIBG scintigraphic abnormalities were found in ten of the twelve patients. The six patients with the VVI pacemaker manifested MIBG scintigraphic abnormalities. These MIBG scintigraphic abnormalities were observed in all segments, particularly in the posterior segments. The mean total defect score of the VVI group was higher than that of the DDD group (14.8 +/- 9.8 vs 3.0 +/- 3.5, respectively p < 0.05). Therefore, we conclude that despite several limitations of the study, MIBG scintigraphic abnormalities occur in patients with implanted permanent pacemakers, and that such abnormalities are more prominent with the VVI than DDD pacemaker.

3-Iodobenzylguanidine↗

A family study of ankylosing spondylitis.

Clinical, radiological and scintigraphic studies and HLA type assessment were performed in 38 subjects, constituting all the first-degree members of three generations of the families of six patients affected with ankylosing spondylitis (AS). The families included both parents, all siblings and all children of the probands. Definite AS was found in three men and possible AS in another. In another man and in a woman, a diagnosis of asymptomatic bilateral sacroiliitis was made. These six subjects indicate a family prevalence of AS reaching 15.8%. HLA B27 was present in 20 individuals (52.6%), including those with definite and possible AS and the case with asymptomatic sacroiliitis. The woman with asymptomatic sacroiliitis lacked HLA B27 antigen. Our study confirms the familial occurrence of AS, but it shows the occurrence to be lower than that previously reported.

Adolescent↗

Correction of respiratory motion in hepatic scintigraphy.

An analog device to correct for respiratory motion was used in 100 consecutive liver scans to determine its clinical utility. The sets of scan images generated were reviewed separately, then together, without knowledge of clinical presentation or imaging technique. When the images were reviewed separately, there was no clinical significant change in patient classification. When the images were reviewed together, 57% of the patients had detectable differences in image features, and in most instances this difference was limited to a clearer definition of organ outline or normal variants (e.g., gallbladder fossa). Of the 17 patients with focal hepatic disease, 14 had these defects better defined or additional lesions identified. Of the 18 patients with definite, diffuse, nonhomogeneous tracer distribution as seen in the uncorrected images, 12 had changes in scan appearance with motion correction. In eight patients the scan pattern became more normal, but in four the abnormal pattern was modified to that of focal defects.

Humans↗

Cerebral blood flow in subcortical global aphasia. Perisylvian cortical hypoperfusion as a crucial role.

BACKGROUND AND PURPOSE: Global aphasia after subcortical stroke is very rare, and its pathophysiology remains unsolved. To clarify the mechanism underlying subcortical global aphasia, we investigated lesion sites and cerebral blood flow in patients with subcortical global aphasia and nonaphasic patients with subcortical stroke. METHODS: We examined four patients with global aphasia and four nonaphasic patients. Language testing was performed more than 4 weeks after the onset. Measurement of cerebral blood flow was done between 35 and 75 days after stroke by using single-photon emission computed tomography (SPECT) with N-isopropyl-p[123I]iodoamphetamine as a tracer and three-dimensional surface display generated from SPECT. RESULTS: All aphasic patients had subcortical lesions in the putamen, posterior internal capsule, temporal isthmus, and periventricular white matter in the left hemisphere. No cortical lesions were found on either magnetic resonance imaging or computed tomographic scanning. The nonaphasic patients had smaller periventricular white matter lesions and no temporal isthmus lesions. All aphasic patients showed cortical hypoperfusion mainly in the perisylvian areas, including Broca's and Wernicke's areas. In contrast, cortical cerebral blood flow of the nonaphasic patients was decreased in smaller areas and spared the perisylvian language areas. CONCLUSIONS: These results suggest that cortical hypoperfusion in the perisylvian language areas, presumably due to undercutting of the white matter, is crucial for the development of subcortical global aphasia.

Aged↗

A dual collimator design for beat-to-beat measurement of cardiac performance with an Anger camera.

A dual collimator was designed for an Anger camera to permit measurement of cardiac performance on a beat-to-beat basis. Special all-purpose (SAP) and special high-sensitivity (SHS) collimator sections can be interchanged without movement of the patient. Thus, left-ventricular regions of interest delineated on SAP multigated images can be transferred to SHS dynamic images to generate beat-to-beat volume curves. Preliminary balloon studies demonstrated an excellent correlation between ejection fractions calculated with the two collimators: r greater than 0.99, n = 17, p less than 0.001. Varying the volume of an adjacent "right ventricle" balloon failed to alter significantly the count rate from the "left ventricle" balloon's region of interest. Preliminary results on 12 patients, comparing standard-camera ejection fractions with average beat-to-beat ejection fractions, showed that is is possible to measure cardiac function on a beat-to-beat basis with a single-crystal gamma camera. There was minimal difference between the ejection fractions calculated by the dual-collimator method and a standard gated technique (r = 0.98, n = 12, p less than 0.001).

Erythrocytes↗

A new method for quantitation of platelet microthrombi and microemboli from cardiopulmonary bypass in organs using 111In labeled platelets.

During cardiopulmonary bypass (CPB), showers of microemboli (ME) distribute among the organs and connective tissues according to regional blood flow. Post CPB, ME were quantified by subtracting residual platelets (RP) in the organs of a group of unoperated control Yorkshire pigs (n = 6) from those of operated pigs. The RP level was minimized by heparinization (300 IU/kg) before death and exsanguination. The number of adherent microthrombi (MT) and ME from the oxygenator (OX), arterial filter (AF), and thoracotomy site were determined using 111In labeled autologous platelets (INPLT) (525-585 microCi administered 24 hr before CPB) in two CPB groups (ACT > 400 sec) of 12 pigs (30-35 kg). CPB was carried out at a flow of 2.5-3.5 L/min at 28 degrees C with a roller or a centrifugal pump, OX (Bentley Univox 1.8 m2), AF (0.25 m2), and cardiotomy reservoir (CR) (Bentley BR: 3,500), for 90 (n = 6) and 180 (CPB 180, n = 6) min. Six pigs underwent thoracotomy without CPB. L-Arginine was infused at a dose of 2 mg/ kg/min during CPB (n = 6). Flow cytometry was used to estimate the circulating ME in blood. MT and organ trapped ME were imaged with a gamma camera and measured with an ion chamber and a gamma counter. ME values (percent of injected INPLT dose) in six organs and four connective tissues were calculated for all five groups. INPLT distribution indicated a uniform distribution of low level platelet MT in the CR and AF. Circulating ME amounted to 2.5% of total platelets. In the CPB circuit, ME generation in AF was the rate-limiting step (n = 4 x 10(5)). Similar studies in organs and tissues suggested the presence of a uniform distribution of the total events of ME (n = 500 x 10(6)). ME increase in brain, lung, liver, and skeletal muscle following thoracotomy and CPB was significant. The low level of ME in ischemia sensitive organs also indicated the presence of a thrombolytic threshold for cumulative ME. ME disaggregation was activated at an early stage to prevent ischemic damage, specifically in the brain. Measurement of trapped ME provided a novel, reliable, and one step method of evaluation of thrombogenicity of a CPB device and drugs.

Animals↗

Applied potential tomography. Noninvasive method for measuring gastric emptying of a solid test meal.

Applied potential tomography (APT) is a new noninvasive, nonradioactive method of measuring gastric emptying, which generates profiles of emptying of liquids that are similar to those obtained simultaneously by scintigraphy and dye dilution. This study validates the ability of APT to measure emptying of a solid beefburger test meal from the stomach by comparing the results obtained with those obtained simultaneously by scintigraphy. When acid secretion was inhibited, there was a significant correlation between the two methods for the time taken for half the meal to empty from the stomach and the amount of meal emptied at different time intervals. Furthermore, the profiles of gastric emptying obtained by APT resembled those obtained by scintigraphy in most studies. If acid secretion was not inhibited, there was no correlation between values obtained by the two methods.

Adult↗

Functionalization of hydroxy compounds with nitrilotriacetic acid for technetium-99m chelation: excretory properties of the radiolabelled chelates.

Substituted monoanilides of nitrilotriacetic acid (NTA) have gained much popularity in recent years as an important class of ligands for technetium-99m (99mTc) radiopharmaceutical preparations used in liver imaging and function studies. We were interested in investigating the properties of the corresponding ester analogues of this important class of ligands and for this study cyclohexanol was selected as a hydroxy component, which on condensation with nitrilotriacetic acid in the presence of acetic anhydride, furnished the monoester, N-cyclohexyloxycarbonylmethyl iminodiacetic acid 4 and the corresponding diester 5. Phenol on similar condensation produced mainly the diester, N,N-di(phenyloxycarbonylmethyl) aminoacetic acid 2, with traces of the corresponding monoester 7. A reinvestigation of the well known condensation reaction of aniline with nitrilotriacetic acid revealed that in addition to the reported monoanilide, N-phenylcarbamoylmethyl imino diacetic acid 3, the corresponding dianilide 6 was also produced in appreciable amount. The ester ligands 2, 4, 5 after 99mTc chelation exhibited good in vitro and in vivo stabilities. The biodistribution characteristics of these radiolabelled esters and amides were very similar showing thereby that esterification with NTA could be an effective method for converting alcohols to 99mTc-radiopharmaceuticals without generating any unusual properties because of the ester linkage. Residual radiopharmaceutical concentration after i.v. administration of these amide and ester 99mTc chelates at 30 min in blood, urine, liver, kidney and intestine were correlated with their lipophilicities and during this correlation it was observed that in addition to lipophilicity the anionic strength of these chelates is also an important determinant in governing their biodistribution. The ester ligand 4 after 99mTc chelation showed ultrafast hepatobiliary kinetics and was therefore compared in a rabbit model with a standard hepatobiliary radiopharmaceutical 99mTc-N-(p-butylphenylcarbamoyl methyl) iminodiacetic acid (99mTc-BIDA) by gamma-camera scintigraphy to investigate the potential of the former for clinical studies.

Animals↗

Characterization of the generation of radiolabeled monodisperse albuterol particles using the spinning-top aerosol generator.

UNLABELLED: Inhaled radiolabeled aerosols provide invaluable information about in vivo drug deposition. Here, we report our methodology for radiolabeling and imaging monodisperse pharmacologic aerosols in order to study basic aerosol science concepts of drug delivery within the human airways. METHODS: We used a spinning-top aerosol generator to produce (99m)Tc-labeled monodisperse albuterol sulfate aerosols of 1.5-, 3-, and 6- micro m mass median aerodynamic diameter. RESULTS: In vitro Andersen cascade validation data showed that technetium and albuterol were coassociated on each impactor stage for all 3 aerosols, and the radiolabeling process itself did not affect their particle size distributions. Good-quality gamma-camera scintigraphic images of lung and extrathoracic deposition were obtained within an asthmatic patient. CONCLUSION: We have successfully radiolabeled and imaged monodisperse albuterol aerosols within the human lungs. This novel technique provides an important tool to relate fundamental concepts of aerosol particle behavior, in vivo deposition, and therapeutic clinical response.

Administration, Inhalation↗

Multiple swallow test for the quantitative and qualitative evaluation of esophageal motility disorders.

Esophageal motility was evaluated from the analysis of six consecutive swallows. A sum image was generated comprising the representative information of an entire study. Calculation of emptying rates and characterization of the bolus behavior was performed from the sum image and the single swallow data. In 86 patients investigated, liquid and solid-phase studies showed a remarkable variation of single swallow data in normals (relative variation coefficient for liquid: 10%, solid: 14%), which were even higher (p less than 0.001) in patients with disorders (liquid: 31%, solid: 25%). As sum images compensate for this intra-individual variation, false-positive (liquid: 16%, solid: 25%) or negative single swallow findings (liquid: 36%, solid: 27%) are reduced. Qualitative analysis of condensed sum images provided characteristic image patterns representing different pathophysiologic aspects. Since the method introduced better discriminates between normal and pathologic function, it may enhance diagnostic accuracy.

Deglutition↗

Xenon-133 hepatic retention ratio: a useful index for fatty liver quantification.

Xenon-133 hepatic retention ratio was developed for quantifying fatty liver. Data were acquired in frame mode in the hepatic region and both lung bases for 5 min after rebreathing 20 mCi of gaseous 133Xe and for another 5 min during washout. Static [99mTc]sulfur colloid liver imaging was performed with the patient in the identical position immediately after the ventilation study and data were stored for liver localization. A hepatic time-activity curve corrected for background activity was generated. The 133Xe retention ratio was derived by dividing the activity at 3.5 min after washout by the peak activity. The data of 16 controls and 20 patients with fatty liver were analyzed. The retention ratio (mean +/- s.d.) was greatly increased in patients with fatty infiltration (0.43 +/- 0.20 vs. 0.04 +/- 0.08 in controls, p less than 0.001). There was a strong positive correlation between the 133Xe retention ratios and percentage of fat on biopsy as assessed by the amount of the liver tissue occupied by fat globules on H & E stained sections. The 133Xe hepatic retention ratio is a simple, accurate and clinically useful index of detecting, quantifying and managing fatty infiltration of the liver.

Adult↗

Cholescintigraphy in the diagnosis and assessment of benign papillary stenosis.

Benign papillary stenosis (BPS) is an uncommon condition, the diagnosis of which is often difficult. In this report cholescintigraphy with technetium-99m diethyl-acetanilido-iminodiacetic acid has been evaluated for the diagnosis of BPS, as well as for assessing the effect of treatment by endoscopic sphincterotomy (ES). In 12 patients with BPS, cholescintigraphy was performed before and after ES and the findings compared with those in ten controls. Time-activity curves from regions over the liver and bowel were generated. A significant difference was found in respect of the time for maximum activity (Tmax) over the liver before and after ES. The time for occurrence of bowel activity (Texcr) also showed significant differences before and after ES. Considering both Tmax and Texcr mean values plus two standard deviations in the control group, all BPS patients would have been detected and there would have been no false-positives among the controls. It is concluded that cholescintigraphy should be used in the diagnosis of BPS. The method has high sensitivity and should be applied as an early diagnostic procedure to exclude BPS in patients with clinical suspicion of the disorder. The method can also be used for assessment of endoscopic treatment (ES).

Aged↗

Design and characterization of alpha-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination.

alpha-Melanocyte stimulating hormone (alpha-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind alpha-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, D-Phe7-alpha-MSH4-13 analog. Structural analysis of the Re-peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate-metal-thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re-peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re-alpha-MSH analog. Characterization of the second-generation Re-peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of alpha-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties.

Amino Acid Sequence↗

T cells migrate to tumour sites after extracorporeal interleukin 2 stimulation and reinfusion in a patient with metastatic melanoma.

Peripheral blood mononuclear cells (PBMC) were taken by leukapheresis from a patient with melanoma skin metastases and stimulated in vitro using 1000 IU recombinant interleukin 2 (IL-2)/ml to generate lymphokine-activated killer cells (LAK cells). Two-colour immunofluorescence analysis demonstrated an IL-2-induced up-regulation of CD25 on natural killer cells (CD56+) as well as on T lymphocytes (CD3+). After radiolabelling with indium-111, the cells were reinfused. Gamma-camera imaging revealed an enrichment at the tumour sites. Immunostaining of tumour tissue taken before and after scintigraphy demonstrated CD25+ T lymphocytes (CD2+, CD3+), but no natural killer cells (CD16+, CD56+) infiltrating the metastases. LAK cell enrichment at melanoma metastases in vivo did not involve natural killer cells, but was characterized by increased numbers of activated T lymphocytes in this patient.

Cell Movement↗

Direct current stimulation of bone production in the horse: preliminary study with a "gap healing" model.

The effect of a 20-microA direct-current implantable bone growth stimulator (BGS) on bone production with a "gap healing" model in the horse was evaluated. The right and left 4th metatarsal bones (Mt-4) were used in 7 adult horses to create the "gap healing" model. A 4-mm section of the Mt-4 bone was resected bilaterally in each horse. The BGS was surgically placed into the 7 left Mt-4 defects. The 7 right Mt-4 defects served as controls. Six horses survived the 16-week experimental period. Signs of pain, decreased range of limb motion, or lameness was not observed in any animal during the 16 weeks. None of the animals showed complete healing radiographically. Four stimulated sites showed less periosteal reaction and 2 showed greater reaction than the 6 controls. The greatest amount of periosteal reaction or bone resorption was seen around the screws and plates in both groups. Uptakes of 99mTc-MDP in counts/pixel for control sites and stimulated sites were 7.90 and 8.25 in the "gap defect" and 5.19 and 5.06 in the areas adjacent to the gap defect. The ratio of uptake between the gap defect and adjacent area was 1.5 and 1.58 respectively. Biocompatability of the BGS was excellent; however, 1 horse had a broken cathode wire 5 cm from the generator capsule at 6 weeks. All polyethylene cathode sheaths were fluid filled at 16 weeks. The average mineralization rates were 1.57 +/- 0.34, 1.71 +/- 0.28 mm/day and bone formation activity was 0.0182 +/- 0.171, and 0.0168 +/- 0.0149 mm2/day for control limbs and stimulated limbs, respectively. There was no significant difference between groups in any of the histomorphometric values measured. Direct current (20 microA) did not increase bone production in this experiment. Methods to objectively evaluate electrically induced osteogenesis and a "gap defect" model for BGS research on the horse are discussed. The results provide a basis for additional research on electrical stimulation of fractures in the horse and for dose-response studies.

Animals↗

Use of positron emission tomography in animal research.

Among the several imaging technologies applied to in vivo studies of research animals, positron emission tomography (PET) is a nuclear imaging technique that permits the spatial and temporal distribution of compounds labeled with a positron-emitting radionuclide to be determined noninvasively. It can be viewed as an in vivo analog of classic autoradiographic methods. Many different positron-labeled compounds have been synthesized as tracers that target a range of specific markers or pathways. These tracers permit the measurement of quantities of biological interest ranging from glucose metabolism to gene expression. PET has been extensively used in imaging studies of larger research animals such as dogs and nonhuman primates. Now, using newly developed high-resolution dedicated animal PET scanners, these types of studies can be performed in small laboratory animals such as mice and rats. The entire whole-body biodistribution kinetics can be determined in a single imaging study in a single animal. This technique should enable statistically significant biodistribution data to be obtained from a handful of animals, compared with the tens or hundreds of animals that might be required for a similar study by autoradiography. PET also enables repeat studies in a single subject, facilitating longitudinal study designs and permitting each animal to serve as its own control in experiments designed to evaluate the effects of a particular interventional strategy. This paper provides a basic overview of the methodology of PET imaging, a discussion of the advantages and drawbacks of PET as a tool in animal research, a description of the latest generation of dedicated animal PET scanners, and a review of a few of the many applications of PET in animal research to date.

Anatomy, Cross-Sectional↗