Low-dose single acquisition rest 99mTc/stress 201Tl myocardial perfusion SPECT protocol: phantom studies and clinical validation

Purpose

We developed and tested a single acquisition rest ^99mTc-sestamibi/stress ²⁰¹Tl dual isotope protocol (SDI) with the intention of improving the clinical workflow and patient comfort of myocardial perfusion single photon emission computed tomography (SPECT).

Methods

The technical feasibility of SDI was evaluated by a series of anthropomorphic phantom studies on a standard SPECT camera. The attenuation map was created by a moving transmission line source. Iterative reconstruction including attenuation correction, resolution recovery and Monte Carlo simulation of scatter was used for simultaneous reconstruction of dual tracer distribution. For clinical evaluation, patient studies were compared to stress ^99mTc and rest ^99mTc reference images acquired in a 2-day protocol. Clinical follow-up examinations like coronary angiography (CAG) and fractional flow reserve (FFR) were included in the assessment if available.

Results

Phantom studies demonstrated the technical feasibility of SDI. Artificial lesions inserted in the phantom mimicking ischaemia could be clearly identified. In 51/53 patients, the image quality was adequate for clinical evaluation. For the remaining two obese patients with body mass index?>?32 the injected ²⁰¹Tl dose of 74 MBq was insufficient for clinical assessment. In answer to this the ²⁰¹Tl dose was adapted for obese patients in the rest of the study. In 31 patients, SDI and ^99mTc reference images resulted in equivalent clinical assessment. Significant differences were found in 20 patients. In 18 of these 20 patients additional examinations were available. In 15 patients the diagnosis based on the SDI images was confirmed by the results of CAG or FFR. In these patients the SDI images were more accurate than the ^99mTc reference study. In three patients minor ischaemic lesions were detected by SDI but were not confirmed by CAG. In one of these cases this was probably caused by pronounced apical thinning. For two patients no relevant clinical follow-up information was available for evaluation.

Conclusion

The proposed SDI protocol has the potential to improve clinical workflow and patient comfort and suggests improved accuracy as demonstrated in the clinical feasibility study.     

Nonuniform transmission in brain SPECT using 201Tl, 153Gd, and 99mTc static line sources: anthropomorphic dosimetry studies and influence on brain quantification.

Nonuniform attenuation correction in brain SPECT can be done routinely by means of additional gamma transmission CT (TCT) measurements, using different commercially available line-source isotopes, 201Tl, 153Gd, and 99mTc are among the most commonly used isotopes, depending on practical and cost-effectiveness issues. We have measured additional radiation burden from static uncollimated brain SPECT transmission sources for these isotopes. The influence of the transmission isotope on brain quantification was also measured and compared with uniform attenuation correction for phantom and human data. Full iterative transmission and emission reconstruction were compared with filtered backprojection techniques. METHODS: Rod sources with 201Tl, 153Gd, and 99mTc were used on a triple-head gamma camera. Dosimetry was performed using LiF TLD-100 pellets and an anthropomorphic RANDO phantom. Effective dose equivalents were calculated on the basis of measured and extrapolated absorbed doses. For brain activity measurements, a Hoffman phantom was used. Images were corrected for scatter (triple-energy window) and were reconstructed by Chang attenuation correction and filtered backprojection as well as full iterative reconstruction (ordered-subsets expectation maximization [OSEM]). To study the effect of inhomogeneous bone attenuation, realistic measurements were performed on 10 young, healthy volunteers with 153Gd TCT. After stereotactic image realignment, a volume-of-interest analysis normalized to total counts was performed. RESULTS: Brain SPECT-TCT using 201Tl, 153Gd, and 99mTc produced total effective dose-rate equivalents of 50.3 +/- 11.2, 32.0 +/- 2.7, and 71.1 +/- 7.1 microSv/GBq x h, respectively, representing dose equivalents of 18.6, 11.9, and 26.3 microSv for a typical 20-min brain SPECT scan at maximal used source strength. Standardized quantification resulted in insignificant differences between the isotopes and methods (Chang versus OSEM) used for nonuniform correction. Iterative reconstruction enhanced image contrast and provided more accurate gray-to-white matter ratios. Between nonuniform and uniform attenuation with an optimized attenuation coefficient, slight central discrepancies were found for volunteer studies. Significantly lower intersubject variation was found for nonuniform corrected values in infratentorial and posterior brain regions. CONCLUSION: Brain transmission scanning using 201Tl, 153Gd, or 99mTc results in limited effective radiation dose equivalents compared with the typical radiation burden. Relative brain perfusion quantification is not significantly different for the various nonuniform TCT isotopes. Iterative reconstruction improves gray-to-white contrasts but has no significant influence on brain perfusion semiquantification. Nonuniform attenuation correction decreases intersubject variability in the posterior brain regions that were compared, which may lead to improved sensitivity toward clinical applications.     

Effects of ouabain on 201Tl and 99mTc MIBI kinetics in rat myocardium--in vivo study using miniature CsI detector]

The aim of this study is to investigate the effect of ouabain (inhibitor of Na-K ATPase) in the myocardial uptake and clearance of 201Tl and 99mTc MIBI using rats. Time activity curves of three groups were measured by CsI miniature detector for 15 min after the administration of each radiopharmaceutical. Groups were divided as follows; 1) control group (CON group), 2) early phase as 15 min after the administration of ouabain (OU15 group), and 3) late phase as 120 min after the administration of ouabain (OU120 group). Main organs of rats including myocardium were resected at 1 min and 15 min after the administration of 201Tl or 99mTc MIBI under the anesthesia of pento-barbital sodium. The uptake (%ID/g) of 201Tl or 99mTc MIBI was measured by well type scintillation counter. The uptake of 201Tl of OU15 group was significantly higher than CON group (OU15: 10.81 +/- 1.90, CON: 1.86 +/- 0.42) and cleared more rapidly. On the contrary, OU120 group showed lower uptake (1.70 +/- 0.21) and slower clearance than OU15 group. Time activity curve of OU15 group indicated the accelerated washout compared with CON group. However, OU120 group showed significantly the reduced washout (CON group: 19%, OU15 group: 22%, OU120 group: 9%). On the other hand, the uptake and time activity curves of 99mTc MIBI were not influenced by ouabain administration. In conclusion, myocardial uptake and clearance of 99mTc MIBI were not related to Na-K ATPase activity, while those of 201Tl were markedly influenced by Na-K ATPase.     

Photon energy recovery for crosstalk correction in simultaneous 99mTc/201Tl imaging.

Simultaneous 99mTc sestamibi/201Tl imaging enables the acquisition of images of myocardial stress perfusion and myocardial viability in a single process. One of the major limits of this technique is the crosstalk of the 99mTc downscattered photons into the 201Tl window. We propose using the spectral deconvolution technique photon energy recovery (PER) for correcting this crosstalk. METHODS: A planar line phantom made of 99Tc vertical lines and 201Tl horizontal lines and a cardiac SPECT phantom including an anterior (2 mL) and an inferior (1.5 mL) myocardial fixed defect were used. The phantoms were filled with an initial 99mTc/201Tl ratio of 5:1. Several successive acquisitions were made from time t = 0 to time t = 48 h (99mTc/201Tl ratio approximately 0) without moving the phantoms. Total number of counts, contrast, and normalized SD (NSD) were calculated on the Tl-raw and the Tl-PER planar images. SPECT datasets were analyzed. The Tl-raw images recorded at 48 h were considered the reference "virgin" 201Tl images. RESULTS: Total number of counts, contrast, and NSD ranged from 336% to 201%, 15% to 29%, and 257% to 225% of the virgin 201Tl values, respectively, for Tl-raw planar images; whereas values for Tl-PER images ranged from 128% to 108%, 61% to 79%, and 154% to 108%, respectively. Anterior and inferior defect contrasts ranged from 1.18 to 1.22 and 1.12 to 1.16 for Tl-raw SPECT images, respectively; whereas for Tl-PER images, value ranges were 1.28-1.32 and 1.21-1.24, respectively. The corresponding reference virgin 201Tl values were 1.31 and 1.25 respectively. Summed score, average defect severity, and average defect extent ranges were 4-5, 0.4-0.52, and 4.7-5.9 for Tl-raw images, respectively, and 8-9, 0.59-0.79, and 7.4-8.8 for Tl-PER images. The reference virgin 201Tl values were 9, 0.73, and 8.7, respectively. CONCLUSION: PER is quantitatively efficient to remove 99mTc crosstalk photons from 201Tl images for 99mTc/201Tl ratios ranging from 5:1 to 2:1.     

Evaluation of simultaneous 201Tl/99mTc dual-isotope cardiac SPECT imaging with model-based crosstalk compensation using canine studies

Background

Simultaneous ²⁰¹Tl/^99mTc-sestamibi dual-isotope myocardial perfusion SPECT imaging can reduce imaging time and produce perfectly registered rest/stress images. However, crosstalk from ^99mTc into ²⁰¹Tl images can significantly reduce ²⁰¹Tl image quality. We have developed a model-based compensation (MBC) method to compensate for this crosstalk. The method has previously been validated with phantom and simulation studies. In this study, we evaluated the MBC method using a canine model.

Methods

Left anterior descending or left circumflex coronary artery stenoses were created in 50 adult mongrel dogs weighing 20-30 kg. The dogs were injected with 111 MBq (3 mCi) of ²⁰¹Tl at rest, and a SPECT study acquired. Stress was induced by administering adenosine to the dog, followed by injection of 740 MBq (20 mCi) of ^99mTc-sestamibi at peak stress. A second SPECT study was performed with data acquired in both ²⁰¹Tl and ^99mTc energy windows to provide simultaneous dual-isotope projection data. The images were reconstructed using the ordered-subsets expectation-maximization reconstruction algorithm with compensation for attenuation, scatter, and detector response. For simultaneously acquired ²⁰¹Tl data, we also applied the MBC method to compensate for crosstalk contamination from ^99mTc.

Results

Without compensation, ^99mTc crosstalk increased the estimated ²⁰¹Tl activity concentration in the rest images and reduced defect contrast. After MBC, the ²⁰¹Tl images were in good agreement with the registered single-isotope images and ex vivo count data. The ischemic (IS) to non-ischemic (NIS) region ²⁰¹Tl activity concentration ratios were computed for single-isotope and dual-isotope studies. The correlation with ex vivo IS-NIS ratios was 0.815 after MBC, compared to the 0.495 from data without compensation. In addition, the regression line for the IS-NIS ratios with MBC was almost parallel to the line of identity with a slope of 0.93, compared to a slope of 0.45 without compensation.

Conclusions

These results demonstrate that model-based crosstalk compensation can provide substantial reduction of crosstalk effects in simultaneously acquired myocardial perfusion SPECT images in living biological systems.     

The quantification of Tl and Cu concentrations in 201Tl solutions using anodic stripping voltammetry

Thallium-201 is a cyclotron produced isotope which is used in nuclear medicine for myocardial function studies. Thallium-201 is prepared by the (p, 3n) reaction on ²⁰³Tl to form ²⁰¹Pb which decays by positron emission to ²⁰¹Tl. Prior to irradiation the thallium target is electro-deposited onto a copper cathode. After irradiation the target is processed by leaching the cathode with dilute acid and passing the leachate through ion exchange resins.Pharmocopoeia monographs on pharmaceutical grade ²⁰¹Tl define limits on the concentrations of Tl and Cu which may be present in solutions of ²⁰¹Tl. It is therefore important from a quality control viewpoint to have a rapid, accurate means of analysis of quantify levels of these metals in radioactive solutions of ²⁰¹Tl.We have developed a procedure utilizing anodic stripping voltammetry to quantify concentrations of Tl and Cu in solutions of ²⁰¹Tl.     

Minimum detectable defect thickness in SPECT myocardial perfusion test: phantom study with (99m)Tc and (201)Tl.

OBJECTIVE: The purpose of this study was to determine experimentally the minimum thickness (D(min)) of a defect inserted on the myocardial wall of a cardiac phantom at different locations that could be clearly detected in a SPECT perfusion study using (99m)Tc and (201)Tl. METHODS: Rectangular (or cylindrical) defects with the same thickness were inserted on the inner surface of a myocardial phantom at 5 different locations: anterior (ANT), septal (SEP), inferoposterior (IP), lateral (LAT), and apical (AP). For different defect thickness (from 1 to 7 mm, in increments of 1 mm) the myocardial SPECT perfusion study was performed with (99m)Tc and (201)Tl using the same protocol that we use for patients. Baseline studies (with no defect inserted) were also performed. The SPECT images of the myocardial phantom with defects were compared with baseline SPECT images to determine whether the defect could be clearly identified. RESULTS: The uniformity of the baseline SPECT images was analyzed very carefully where an IP artifact was detected. The D(min) was determined for (99m)Tc and (201)Tl at 3 radii of rotation: 21.0, 25.0, and 29.2 cm. CONCLUSION: To be detected on SPECT images, a defect must be of a thickness > or =D(min). A simple method for performing a quality control test for SPECT nuclear cardiology can be developed based on these findings.     

Diaphyseal medullary stenosis with pleomorphic malignant fibrous histiocytoma of the bone:99mTc hydroxymethylenediphosphonate and201Tl chloride scintigraphy findings

Diaphyseal medullary stenosis (DMS) is an extremely rare hereditary bone dysplasia, which was first described by Arnold in 1973. DMS has a high incidence of pleomorphic malignant fibrous histiocytoma (MFH). In this paper, we report the imaging findings of DMS with pleomorphic MFH of the bone, mainly describing 99mTc hydroxymethylenediphosphonate (HMDP) and thallium-201 (201Tl) chloride scintigraphy findings. On 99mTc HMDP scintigraphy, focal increased uptake area of the right femur corresponded to the area of bone marrow invasion of the tumor and bone infarction. The mechanism of the uptake of 99mTc HMDP to the extraosseous lesion was not clear. On 201Tl chloride scintigraphy, the increased uptake of the periphery of the mass seemed to reflect the aggressiveness of invasion and the cellularity.     

Quantitative evaluation for scatter and attenuation correction in 99mTc SPECT--multicenter cooperation phantom study

A multicenter cooperation phantom study was conducted to evaluate the accuracy of a triple energy window scatter correction technique in combination with various attenuation correction methods for 99mTc single photon emission computed tomography (SPECT) imaging. Six centers participated in this research and the data obtained with seven SPECT instruments were analyzed. The phantom used in the experiment was a 20 x 10 cm cylinder filled with homogeneous 99mTc solution, containing two kinds of cold spots (cold rod phantoms). One had a water-filled cylinder 5.5 cm in diameter positioned 2.5 cm from the center. The other contained 6 water-filled cylinders of various sizes. Contrasts of cold regions were in the range from 74% to 120% (true 100%). Another phantom had the shape of a pie-chart divided into six chambers symmetrically positioned in a cylinder 20 cm in diameter and 10 cm in height. Each chamber had volume of 480 ml and contained homogeneous 99mTc solution of different concentrations. This phantom was used to test for linearity between the radio activity concentration and reconstructed count density (linearity phantom). The intercept of the regression line obtained from the linearity phantom was 8.4 kBq ml-1 without scatter correction and -6.8 kBq ml-1 with scatter correction. Contrast was in the range from 78% to 132% (true 100%). The mean relative error for the measured activity concentration was 4.9% +/- 3.5% (mean +/- sd).     

Rapid myocardial perfusion imaging with 99Tcm-teboroxime and a three-headed SPECT system: a comparative study with 201Tl.

99Tcm-teboroxime is a new myocardial perfusion agent with a high first pass extraction and rapid myocardial washout. The usefulness of 99Tcm-teboroxime was evaluated for detection of myocardial ischaemia using a three-headed single photon emission tomography (SPECT) system which allows for rapid data acquisition. The subjects consisted of 14 patients, including seven with ischaemic heart disease, four with cardiomyopathy and three others. After the 99Tcm-teboroxime injection, dynamic data was collected every minute for 15 min with continuous rotation. High-quality SPECT images could be obtained by reconstructing the serial scans from 2 to 8 min. The sensitivity, specificity and accuracy of the 99Tcm-teboroxime study for the detection of the ischaemic region were not significantly different from those of the 201Tl study. Myocardial clearance was slow in the ischaemic lesion and in the myocardium of cardiomyopathy patients, while the coronary angiograms did not show any abnormality. These results therefore indicate that the rapid SPECT imaging and myocardial clearance of 99Tcm-teboroxime obtained with a three-headed SPECT system were useful for the detection of myocardial ischaemia.     

Low-flow ischaemia has no deleterious effect on the steady-state kinetics of 201Tl and 99mTc sestamibi within myocardial tissue

OBJECTIVES: This study aimed to specifically analyse the impact of low-flow ischaemia on the ability of myocytes to trap and accumulate Tl and sestamibi (MIBI) within myocardial tissue. METHODS: In order to reach steady-state conditions for the interstitial/cellular concentration ratios (Ci/Cc) of the tracers and thereby simulate the conditions of cell cultures studies, Tl and MIBI were injected continuously during an 80 min period within the coronary circulation of isolated hearts submitted to normoxia (n=7) or low-flow ischaemia (n=7; >50% reduction in coronary flow). Ci was determined by using interstitial microdialysis and Cc was determined from Ci and myocardial retention values of the tracers. RESULTS: At the end of the experiments, under steady-state conditions, Ci/Cc was equivalent between low-flow ischaemia and normoxia for both Tl (ischaemia, 0.60 +/- 0.25% vs normoxia, 0.63 +/-0.34%; NS) and MIBI (ischaemia, 1.00 +/- 0.68% vs normoxia, 0.76 +/- 0.32%, NS), whereas tissue concentrations of ATP were more than 4-fold lower in ischaemia than in normoxia (5.1 +/- 3.5 nmol.g vs 22.5 +/- 4.8 nmol.g; P< 0.001). CONCLUSIONS: In contrast to the published results concerning the effects of anoxia on cell cultures, low-flow ischaemia within myocardial tissue has no deleterious effects on the ability of the cells to accumulate Tl and MIBI under steady-state conditions. This gives definitive evidence of the negligible impact of cellular metabolic disorders in the decrease in Tl or MIBI uptake, which is documented by stress-SPECT within low-flow ischaemic myocardium.     

Comparison of99mTc(V)-DMSA,201Tl and99mTc-MIBI imaging in the follow-up of patients with medullary carcinoma of the thyroid

Radionuclide scanning with tumour-seeking agents such as pentavalent technetium-99m dimercaptosuccinic acid [^99mTc(V)-DMSA], thallium-201 and technetium-99m sestamibi (MIBI) has been reported to be useful in the detection of medullary thyroid carcinoma (MTC). We undertook a study in 14 MTC patients to determine the comparative imaging potential of²⁰¹Tl, MIBI and^99mTc(V)-DMSA in the detection of recurrent or metastatic MTC. All patients underwent total thyroidectomy and had persistently elevated serum calcitonin levels after the surgery. Scintigraphic studies were carried out 20 min after the injection of 111 MBq of²⁰¹Tl or 555 MBq of MIBI and 2 h following the injection of 370 MBq of^99mTc(V)-DMSA. All scintigraphic findings were correlated with contemporaneous CT or MRI studies. CT, MRI and bone scans showed 42 (26 bone, 16 soft tissue) metastatic sites in 11 of the 14 patients. In the remaining three patients no lesions were detected during diagnostic evaluation.^99mTc(V)-DMSA showed all of the soft tissue metastases but could not show two bone lesions. On the other hand, MIBI imaging was false-negative in 22 (52%) sites and²⁰¹Tl was false-negative in 34 (80%) sites. Overall, lesion detection sensitivities for^99mTc(V)-DMSA, MIBI and²⁰¹Tl were 95%, 47% and 19% respectively. We conclude that^99mTc(V)-DMSA is clearly superior to MIBI and²⁰¹Tl in the follow-up of MTC patients.     

Acute myocardial infarction imaged with 99mTc-stannous pyrophosphate and 201Tl: a clinical evaluation.

Twenty-six patients suspected of having acute myocardial infarction (AMI) underwent myocardial scintigraphy sequentially with 201Tl and 99mTc-stannous pyrophosphate (99mTc-PPi). Of the 26 patients, 24 had AMI documented by enzyme and electrocardiographic changes. Nineteen had transmural and five had subendocardial myocardial infarctions. The remaining two patients had "unstable angina pectoris." The mean time from onset to imaging was 4 days. Of the 24 patients with AMI, 22 had positive 99mTc-PPi scintigrams. In 20 the area of acute myocardial damage appeared to be the same by 99mTc-PPi scintigram as by ECG; in two, the location could not be precisely determined. The two patients with negative 99mTc-PPi scintigrams at the time of combined myocardial imaging had had positive 99mTc-PPi images previously. In all 24 patients, the 201Tl images were abnormal in at least the location suggested by the electrocardiogram. In seven patients, the area of decreased 201Tl activity was grossly equal to the positive area on the 99mTc-PPi images; in 15, the 201Tl defect was definitely larger; and in two, the 201Tl defect appeared slightly smaller. Although the 99mTc-PPi and 201Tl myocardial images provide different information, both are valuable in determining the overall integrity of the myocardium in patients with ischemic heart disease.     

The efficacy of thallium 201, 99mTc phosphates, and 99mTc MAA in localizing small myocardial infarctions in the pig.

An intercomparison was made of technetium phosphates, thallium 201, and technetium-labeled MAA to define areas of small myocardial infarction in pigs. Byinstilling 0.01 ml of mercury into the coronary arteries, 2-cm infarcts were created. Several of the infarcts were in the anterior left ventricular wall. None of the infarcts was imaged with 99mTc phosphates. Three of the seven thallium 201 images demonstrated only diffuse right ventricular activity. Three of the seven infarcts were imaged with technetium MAA; a perfusion defect was seen in the area of infarction. Technetium MAA is the most sensitive agent in defining areas of abnormal myocardial perfusion.     

A new method for quantification of hepatobiliary scintigraphy using 99mTc-mebrofenin. A comparative study

A method based upon the application of mathematical techniques of deconvolution on the classical compartmental model for the quantitative study of liver function from hepatobiliary scintigraphy using 99mTc-mebrofenin data is proposed. The theory in which the method is based upon is presented and a comparison with a published methodology of obtaining the hepatic extraction after scintigraphic sudies has been performed using the results on 36 rats studies obtained with the two methods. A highly significant correlation between the two techniques was verified. The characteristics of the two methodologies, the proposed one based upon a theoretical approach and the other one on an empirical approximation are discussed. Comments are made on the interest and limitations of the presented technique that may be an useful tool for the evaluation of hepatic insufficiency.     

Differential renal uptake of 201Tl: requirements for acquisition, display and quantification.

Renal uptake of 201Tl may have a role in screening for renal asymmetry in hypertensive patients (HP) who are referred for myocardial scintigraphy. The qualitative aspects of digitized planar images, and quantified differential renal uptake (DRU) of 201Tl were rated by comparing a simple technique (S) for outlining each kidney with an interpolative background subtracted technique (IB). These parameters were assessed in an initial series of patients by varying the length of acquisition (from 1 to 5 min), delay in acquisition (from 10 to 210 min after injection), and image preparation (nine-point smoothing). Six blinded observers rated the quality of coded images. Image quality was improved (P less than 0.01) by increasing the length of acquisition to at least 2 min, by smoothing of the images and by imaging within 2 h of 201Tl injection. Variability in quantification of DRU was suboptimal with acquisition for only 1 min and was more adversely affected with S than with IB. Clinical application of the quantitative technique was assessed in 180 HP and 32 normotensive controls. With IB, the normal range for DRU was slightly greater than for S. The two techniques were comparable in identifying abnormal cases and found 21 +/- 3% (S) and 19 +/- 3% (IB) of HP as lying outside the normal 99% confidence interval. Both quantitative techniques showed excellent agreement with renal angiography (n = 24). Furthermore, preliminary experience with surface markers and with 180 degrees tomography suggests the potential for simultaneous correction for renal depth. These data justify the use of adjunctive renal imaging during myocardial scintigraphy with 201Tl.     

Determination of [201Tl]Tl(III) in [201Tl]TlCl solutions using HPLC.

A high-performance liquid chromatography technique has been presented to measure the [(201)Tl]TlCl(3) impurity in [(201)Tl]TlCl radiopharmaceutical for precise determination of radiochemical purity. Diethylene tetraamine pentaacetic acid (DTPA) has been used for complete complexation of [(201)Tl]Tl(III). [(201)Tl]Tl(III)-DTPA was analyzed in the presence of [(201)Tl]Tl(I) using a cation exchange HPLC column.