Dual-isotope Single-photon Emission Computed Tomography Research Articles

Optimization of 201Tl Dosage in a Simultaneous Acquisition Rest 99mTc/Stress 201Tl Dual-Isotope Myocardial Perfusion Single-Photon Emission Computed Tomography with Semiconductor Gamma Camera.

Background: The use of 201Tl in myocardial perfusion single-photon emission computed tomography (SPECT) is predominantly not recommended because of the higher radiation exposure of 201Tl compared to 99mTc agent. However, the advent of new gamma cameras with semiconductor detectors has made it possible to reduce the 201Tl dose and lower radiation exposure. In our hospital, the dose of 201Tl is adjusted according to the patient's body mass index (BMI), with 50 MBq for BMI<25 and 74 MBq for BMI≥25. The dose of 201Tl during simultaneous acquisition dual-isotope myocardial perfusion SPECT (MPS; stress 201Tl and rest 99mTc agent) exceeds 9 mSv/examination when 74 MBq of 201Tl is administered. In order to further reduce the radiation dose, optimization of the 201Tl dose was investigated. Methods: Two hundred and eighty consecutive patients who underwent stress MPS using simultaneous acquisition dual-isotope protocol (SDI protocol) for the estimation of ischemic heart disease were included. Patients with prior myocardial infarction were excluded. Correlations between BMI and acquisition time were determined in patients receiving 50 MBq (n=154) or 74 MBq (n=126) of 201Tl. In addition, linear regression analysis was used to determine the slope and intercept to derive a linear functional equation, and the theoretically optimal 201Tl dose was evaluated. Results: The correlation coefficient between BMI and acquisition time in the 201Tl 50 MBq group was 0.532 (P< 0.00001) and in the 201Tl 74 MBq group was 0.478 (P<0.00001), both showing a positive correlation. Linear regression analysis yielded two equations: y=0.52x-0.32 (201Tl 50 MBq group) and y=0.41x-0.69 (201Tl 74 MBq group). Linear function equation results indicated that patients with BMI between 25 and 30 could be examined within approximately 15 minutes with 50 MBq of 201Tl. Conclusion: Considering examination efficiency, a single acquisition time of less than 15 minutes is ideal. Theoretically, patients with BMI less than 30 could be examined within approximately 15 minutes with 50 MBq of 201Tl.

Simultaneous assessment of myocardial perfusion and adrenergic innervation in patients with heart failure by low-dose dual-isotope CZT SPECT imaging

BackgroundIn patients with heart failure (HF) sequential imaging studies have demonstrated a relationship between myocardial perfusion and adrenergic innervation. We evaluated the feasibility of a simultaneous low-dose dual-isotope 123I/99mTc-acquisition protocol using a cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera. Methods and resultsThirty-six patients with HF underwent simultaneous low-dose 123I-metaiodobenzylguanidine (MIBG)/99mTc-sestamibi gated CZT-SPECT cardiac imaging. Perfusion and innervation total defect sizes and perfusion/innervation mismatch size (defined by 123I-MIBG defect size minus 99mTc-sestamibi defect size) were expressed as percentages of the total left ventricular (LV) surface area. LV ejection fraction (EF) significantly correlated with perfusion defect size (P < .005), innervation defect size (P < .005), and early (P < .05) and late (P < .01) 123I-MIBG heart-to-mediastinum (H/M) ratio. In addition, late H/M ratio was independently associated with reduced LVEF (P < .05). Although there was a significant relationship (P < .001) between perfusion and innervation defect size, innervation defect size was larger than perfusion defect size (P < .001). At multivariable linear regression analysis, 123I-MIBG washout rate (WR) correlated with perfusion/innervation mismatch (P < .05). ConclusionsIn patients with HF, a simultaneous low-dose dual-isotope 123I/99mTc-acquisition protocol is feasible and could have important clinical implications.

Prediction for cardiac prognosis in patients with congestive heart failure by machine learning on dual-isotope myocardial semiconductor SPECT

Abstract Background Dual-isotope (low doze 201TlCl and 123I-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP)) single photon emission computed tomography (SPECT) is utilized to estimate myocardial damage in patients with congestive heart failure (CHF). However, predictive model construction on the SPECT for cardiac death by machine learning was not studied. Purpose To elucidate predictive value of machine learning model on dual-isotope SPECT for CHF. Methods We enrolled consecutive 310 patients who admitted with CHF (77.1±3.1 years, 164 males). After initial treatment, they underwent electrocardiography gated SPECT and observed in median 507 days [IQR: 165, 1032]. Multivariate Cox regression analysis for cardiac death was performed, and predictive model was constructed by ROC curve analysis and machine learning (Random Forest and Deep Learning). The accuracies (= [True positive + True negative] / Total) of the prediction models were compared with ROC curve model. Results Thirty-six patients fell into cardiac death. Cox analysis showed Age, left ventricular ejection fraction (LVEF), summed rest score (SRS) of BMIPP, and mismatch score were significant predictors (Hazard ratio: 1.068, 0.970, 1.032, 1.092, P value: &amp;lt;0.001, 0.014, 0.002, &amp;lt;0.001, respectively). ROC curve analysis of them revealed the accuracy of the cut-off value was 0.479–0.773. Conversely, machine learning model demonstrated higher accuracy for cardiac death (Random Forest: 0.895, Deep Learning: 0.935). The top 4 feature importance of the random forest were LVEF (0.299), SRS BMIPP (0.263), Age (0.262), and mismatch score (0.160). Conclusion Machine learning model on SPECT was superior to conventional statistic model for predicting cardiac death in patients with CHF. Funding Acknowledgement Type of funding source: None

A Monte Carlo study to investigate the feasibility of an on-board SPECT/spectral-CT/CBCT imager for medical linear accelerator.

The on-board flat-panel cone-beam computed tomography (CBCT) lacks molecular/functional information for current online image-guided radiation therapy (IGRT). It might not be adequate for adaptive radiation therapy (ART), particularly for biologically guided tumor delineation and targeting which might be shifted and/or distorted during the course of RT. A linear accelerator (Linac) gantry-mounted on-board imager (OBI) was proposed using a single photon counting detector (PCD) panel to achieve single photon emission computed tomography (SPECT), energy-resolved spectral CT, and conventional CBCT triple on-board imaging, which might facilitate online ART with an addition of volumetric molecular/functional imaging information. The system was designed and evaluated in the GATE Monte Carlo platform. The OBI system including a kV-beam source and a pixelated cadmium zinc telluride (CZT) detector panel mounted on a medical Linac orthogonally to the MV beam direction was designed to obtain online CBCT, spectral CT, and SPECT tri-modal imaging of patients in the treatment room. The spatial resolutions of the OBI system were determined by imaging simulated phantoms. The CBCT imaging was evaluated by a simulated contrast phantom. A PMMA phantom containing gadolinium was imaged to demonstrate quantitative imaging of spectral-CT/CBCT of the system. The capability of tri-modal imaging of the OBI was demonstrated using three different spectral CT imaging methods to differentiate gadolinium, gold, calcium within simulated PMMA and the SPECT to image radioactive 99m Tc distribution. The dual-isotope SPECT imaging of the system was also evaluated by imaging a phantom containing 99m Tc and 123 I. The radiotherapy-related parameters of iodine contrast fraction and virtual non-contrast (VNC) tissue electron density in the Kidney1 inserts of a simulated phantom were decomposed using the Bayesian eigentissue decomposition method for contrast-enhanced CBCT/spectral-CT of the OBI in a single scan. The spatial resolutions of CBCT and SPECT of the OBI were determined to be 15.1lp/cm at 10% MTF and 4.8-12mm for radii of rotation of 10-40cm, respectively. In CBCT image of the contrast phantom, most of the soft-tissue inserts were visible with sufficient spatial structure details. As compared to the CBCT image of gadolinium, the spectral CT image provided higher image contrasts. Calcium, gadolinium, and gold were separated well by using the spectral CT material imaging methods. The reconstructed distribution of 99m Tc agreed with the spatial position within the phantom. The two isotopes were separated from each other in dual-isotope SPECT imaging of the OBI. The iodine fractions and the VNC electron densities were estimated in the iodine-enhanced Kidney1 tissue inserts with reasonable RMS errors. The main procedures of the tri-modal imaging guided online ART workflow were presented with new functional features included. Using a single photon counting CZT detector panel, an on-board SPECT, spectral CT, and CBCT tri-modal imaging could be realized in Linacs. With the added online molecular/functional imaging obtained from the new OBI for the online ART proposed, the accuracy of radiation treatment delivery could be further improved.

Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach

PurposeAtherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acquisition protocol to assess each radiotracer’s capability to identify plaque phenotype and inflammation levels pertaining to leukocytes expressing leukocyte function-associated antigen-1 (LFA-1) and the leukocyte subset of proinflammatory macrophages expressing somatostatin receptor subtype-2 (SST2). Individual radiotracer uptake was quantified and the presence of corresponding immunohistological cell markers was assessed.MethodsHuman symptomatic carotid plaque segments were obtained from endarterectomy. Segments were incubated in dual-isotope radiotracers [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt) and [99mTc]Tc-[N0–14,Asp0,Tyr3]-octreotate ([99mTc]Tc-Demotate 2) before scanning with SPECT/CT. Plaque phenotype was classified as pathological intimal thickening, fibrous cap atheroma or fibrocalcific using histology sections based on distinct morphological characteristics. Plaque segments were subsequently immuno-stained with LFA-1 and SST2 and quantified in terms of positive area fraction and compared against the corresponding SPECT images.ResultsFocal uptake of co-localising dual-radiotracers identified the heterogeneous distribution of inflamed regions in the plaques which co-localised with positive immuno-stained regions of LFA-1 and SST2. [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake compared with fibrocalcific plaques and pathological intimal thickening phenotypes, in line with the immunohistological analyses.ConclusionA dual-isotope acquisition protocol permits the imaging of multiple leukocyte subsets and the pro-inflammatory macrophages simultaneously in atherosclerotic plaque tissue. [111In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype.

Imaging of Tumor Spheroids, Dual-Isotope SPECT, and Autoradiographic Analysis to Assess the Tumor Uptake and Distribution of Different Nanobodies

PurposeRecent studies have shown rapid accumulation of nanobodies (NBs) in tumors and fast clearance of the unbound fraction, making NBs exceptional tracers for cancer imaging. In this study, we investigate the combination of in vitro imaging of tumor spheroids, in vivo dual-isotope single-photon emission computed tomography (SPECT), and ex vivo autoradiographic analysis of tumors to efficiently, and with few mice, assess the tumor uptake and distribution of different NBs.ProceduresThe irrelevant NB R2 (16 kDa) and the EGFR-targeted NBs 7D12 (16 kDa) and 7D12-R2 (32 kDa) were investigated. Confocal microscopy was used to study the penetration of the NBs into A431 tumor spheroids over time, using the anti-EGFR monoclonal antibody (mAb) cetuximab (150 kDa) as a reference. Dual-isotope [111In]DOTA-NB/[177Lu]DOTA-NB SPECT was used for longitudinal imaging of multiple tracers in the same animal bearing A431 tumor xenografts. Tumor sections were analyzed using autoradiography.ResultsNo binding of the irrelevant NB was observed in spheroids, whereas for the specific tracers an increase in the spheroid’s covered area was observed over time. The NB 7D12 saturated the spheroid earlier than the larger, 7D12-R2. Even slower penetration was observed for the large mAb. In vivo, the tumor uptake of 7D12 was 19-fold higher than R2 after co-injection in the same animal, and 2.5-fold higher than 7D12-R2 when co-injected. 7D12-R2 was mainly localized at the rim of tumors, while 7D12 was found to be more evenly distributed.ConclusionsThis study demonstrates that the combination of imaging of tumor spheroids, dual-isotope SPECT, and autoradiography of tumors is effective in comparing tumor uptake and distribution of different NBs. Results were in agreement with published data, highlighting the value of monomeric NBs for tumor imaging, and re-enforcing the value of these techniques to accurately assess the most optimal format for tumor imaging. This combination of techniques requires a lower number of animals to obtain significant data and can accelerate the design of novel tracers.

The influence of gravity on regional lung blood flow in humans: SPECT in the upright and head-down posture.

Previous studies in humans have shown that gravity has little influence on the distribution of lung blood flow while changing posture from supine to prone. This study aimed to evaluate the maximal influence of posture by comparison of regional lung blood flow in the upright and head-down posture in 8 healthy volunteers, using a tilt table. Regional lung blood flow was marked by intravenous injection of macroaggregates of human albumin labeled with 99mTc or 113mIn, in the upright and head-down posture, respectively, during tidal breathing. Both radiotracers remain fixed in the lung after administration. The distribution of radioactivity was mapped using quantitative single photon emission computed tomography (SPECT) corrected for attenuation and scatter. All images were obtained supine during tidal breathing. A shift from upright to the head-down posture caused a clear redistribution of blood flow from basal to apical regions. We conclude that posture plays a role for the distribution of lung blood flow in upright humans, and that the influence of posture, and thereby gravity, is much greater in the upright and head-down posture than in horizontal postures. However, the results of the study demonstrate that lung structure is the main determinant of regional blood flow and gravity is a secondary contributor to the distribution of lung blood flow in the upright and head-down positions.NEW & NOTEWORTHY Using a dual-isotope quantitative SPECT method, we demonstrated that although a shift in posture redistributes blood flow in the direction of gravity, the results are also consistent with lung structure being a greater determinant of regional blood flow than gravity. To our knowledge, this is the first study to use modern imaging methods to quantify the shift in regional lung blood flow in humans at a change between the upright and head-down postures.

Monte Carlo-based scatter correction considering the tailing effect of a CdTe detector for dual-isotope brain SPECT imaging

A Monte Carlo (MC)-based scatter correction method considering the tailing effect of a CdTe detector was developed for dual-isotope brain single-photon emission computed tomography (SPECT) imaging using technetium-99m (99mTc) and iodine-123 (123I), and its accuracy was validated by measuring phantoms. The tailing effect was modeled by convolutions of energy spectra obtained by geometry and tracking (GEANT) simulation with energy smoothing kernels. In our experimental phantom studies, quantitative accuracy and image contrast in the reconstructed image of dual-isotope-filled phantoms with our MC-based scatter correction method (Dual_SC) were compared with those of single-isotope-filled phantoms (Single_SC). The quantitative accuracy was evaluated by the percent error between the estimated activity concentration and true activity concentration. In our six-compartment phantom study with six different activity concentrations, the mean absolute percent errors of 99mTc for Single_SC and Dual_SC were 1.7% and 2.8%, respectively, while those of 123I for Single_SC and Dual_SC were 4.8% and 5.6%, respectively. In our striatal phantom study, the percent errors in the background regions for Single_SC and Dual_SC were less than 2% for both 99mTc and 123I. The image contrast was evaluated by the percent contrast of a cold or hot spot region to a background region. In our cold rod phantom study, the mean percent contrasts in the cold rod regions of 99mTc for Single_SC and Dual_SC were 66.2% and 65.0%, respectively, while those of 123I for Single_SC and Dual_SC were 59.3% and 61.6%, respectively. In our striatal phantom study, the percent contrasts in the striatal regions of 99mTc for Single_SC and Dual_SC were 56.1% and 56.1%, respectively, while those of 123I for Single_SC and Dual_SC were 39.8% and 40.0%, respectively. In conclusion, dual-isotope imaging with the CdTe-based brain SPECT system and our MC-based scatter correction method can provide comparable quantitative accuracy and image contrast to those of single-isotope imaging.

Simultaneous &lt;sup&gt;99m&lt;/sup&gt;tc/&lt;sup&gt;111&lt;/sup&gt;in spect reconstruction using accelerated convolution-based forced detection monte carlo

Simultaneous multi-isotope Single Photon Emission Computed Tomography (SPECT) imaging has a number of applications in cardiac, brain, and cancer imaging. The major concern however, is the significant crosstalk contamination due to photon scatter between the different isotopes. The current study focuses on a method of crosstalk compensation between two isotopes in simultaneous dual isotope SPECT acquisition applied to cancer imaging using $^{99m}$ Tc and $^{111}$ In. We have developed an iterative image reconstruction technique that simulates the photon down-scatter from one isotope into the acquisition window of a second isotope. Our approach uses an accelerated Monte Carlo (MC) technique for the forward projection step in an iterative reconstruction algorithm. The MC estimated scatter contamination of a radionuclide contained in a given projection view is then used to compensate for the photon contamination in the acquisition window of other nuclide. We use a modified ordered subset-expectation maximization (OS-EM) algorithm named simultaneous ordered subset-expectation maximization (Sim-OSEM), to perform this step. We have undertaken a number of simulation tests and phantom studies to verify this approach. The proposed reconstruction technique was also evaluated by reconstruction of experimentally acquired phantom data. Reconstruction using Sim-OSEM showed very promising results in terms of contrast recovery and uniformity of object background compared to alternative reconstruction methods implementing alternative scatter correction schemes (i.e., triple energy window or separately acquired projection data). In this study the evaluation is based on the quality of reconstructed images and activity estimated using Sim-OSEM. In order to quantitate the possible improvement in spatial resolution and signal to noise ratio (SNR) observed in this study, further simulation and experimental studies are required.

Simultaneous dual-isotope imaging based on an artificial neural network for evaluating myocardial perfusion and fatty acid metabolism

BackgroundWe contrived a scatter correction method based on an artificial neural network (ANN) and applied it to the simultaneous evaluation of myocardial perfusion and fatty acid metabolism in single-photon emission computed tomography (SPECT). MethodsThe count data of three energy windows were used as inputs of the ANN. The count ratios of the estimated primary-to-total photons for 99mTc and 123I, which were used to reconstruct 99mTc and 123I images, were calculated using the ANN. In a phantom study, single- and dual-isotope imaging with 99mTc/123I and 201Tl/123I was performed by means of a cardiac phantom simulating patients with and without obesity. In a human study, five normal volunteers and ten patients with myocardial infarction underwent myocardial perfusion and fatty acid metabolism imaging with single and dual SPECT with combinations of 99mTc-methoxyisobutylisonitrile/123I-beta-methyl(p-iodophenyl)pentadecanoic acid (BMIPP) and 201Tl/123I-BMIPP as tracers. ResultsTechnetium-99m yielded more homogeneous images than 201Tl because of the lower degree of photon attenuation, especially in the condition of obese patients, resulting in clearer visualization of the perfusion-metabolism mismatch. Dual 99mTc/123I SPECT offered comparable images with single SPECT in assessing myocardial damage. ConclusionsThe method effectively separated 99mTc and 123I primary photons and proved applicable to 99mTc/123I dual-isotope myocardial SPECT.

Quantitative image reconstruction for dual-isotope parathyroid SPECT/CT: phantom experiments and sample patient studies

We investigated the quantitative accuracy of the model-based dual-isotope single-photon emission computed tomography (DI-SPECT) reconstructions that use Klein–Nishina expressions to estimate the scattered photon contributions to the projection data. Our objective was to examine the ability of the method to recover the absolute activities pertaining to both radiotracers: Tc-99m and I-123. We validated our method through a series of phantom experiments performed using a clinical hybrid SPECT/CT camera (Infinia Hawkeye, GE Healthcare). Different activity ratios and different attenuating media were used in these experiments to create cross-talk effects of varying severity, which can occur in clinical studies. Accurate model-based corrections for scatter and cross-talk with CT attenuation maps allowed for the recovery of the absolute activities from DI-SPECT/CT scans with errors that ranged 0–10% for both radiotracers. The unfavorable activity ratios increased the computational burden but practically did not affect the resulting accuracy. The visual analysis of parathyroid patient data demonstrated that our model-based processing improved adenoma/background contrast and enhanced localization of small or faint adenomas.

Randomized and double-blind controlled clinical trial of extracorporeal cardiac shock wave therapy for coronary heart disease

Our aim was to evaluate the safety and effectiveness of extracorporeal cardiac shock wave therapy (CSWT) for the patients with coronary heart disease (CHD) using a randomized, double-blind, controlled clinical trial design. Twenty-five patients with CHD were enrolled in this study. Fourteen of the patients were randomized into the CSWT group and 11 into the control group. We applied the CSWT procedure to each patient by using nine shock treatments during 3 months, but the shock wave (SW) energy was only applied to the patients in the CSWT group and not to the patients in the control group. Technetium-99m sestamibi myocardial perfusion, fluorine-18 fluorodeoxyglucose myocardial metabolism single-photon emission computed tomography (SPECT), and two-dimensional echocardiography were performed to identify segments of myocardial ischemia, myocardial viability, and ejection fraction before and after CSWT. We also followed the patients to evaluate adverse effects. After CSWT, the New York Heart Association class, the Canadian Cardiovascular Society angina scale, nitroglycerin dosage, myocardial perfusion and myocardial metabolic imaging scores of dual-isotope SPECT in the CSWT group were reduced significantly (P = 0.019, 0.027, 0.039, 0.000, 0.001, respectively), and the Seattle Angina Questionnaire scale, 6-min walking test, and left ventricular ejection fraction were increased significantly (P = 0.021, 0.024, 0.016, respectively) compared with those before the SW treatment. All of the parameters in the control group did not change significantly after the treatment (all P > 0.05). No serious adverse effects of CSWT were observed. Cardiac shock wave therapy is a safe and effective treatment for CHD patients.

Male breast uptake of 99m-Tc sestamibi in myocardial perfusion imaging

Standard interpretation of single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) studies include analysis of the rest and stress perfusion images as well as evaluation of left ventricular function. However, it is also important to carefully review the rotating cinematic raw projections “rotatograms” for factors that may influence the interpretation and non-cardiac findings. Non-cardiac findings from rotating cinematic images have identified both benign and malignant conditions [ 1 Williams K.A. Hill K.A. Sheridan C.M. Noncardiac findings on dual-isotope myocardial perfusion SPECT. J Nucl Cardiol. 2003; 10: 395-402 Google Scholar , 2 Jones S.E. Aziz K. Yasuda T. Gewirtz H. Scott J.A. Importance of systematic review of rotating projection images from Tc99m-sestamibi cardiac perfusion imaging for noncardiac findings. Nucl Med Commun. 2008; 29: 607-613 Google Scholar ]. We report two male patients who underwent stress technetium 99m sestamibi SPECT and were found to have increased focal tracer uptake identified in the breast region on the rotating cine images; case 1 had a diagnosis of invasive ductal adenocarcinoma of the breast and case 2 had bilateral gynecomastia.

Dual-isotope single-photon emission computed tomography for dopamine and serotonin transporters in normal and parkinsonian monkey brains

Parkinson's disease (PD) affects both dopaminergic and serotonergic systems. In this study, we simultaneously evaluated dopamine and serotonin transporters in primates using dual-isotope single-photon emission computed tomography (SPECT) imaging and compared the results with traditional single-isotope imaging. Four healthy and one 6-OHDA-induced PD monkeys were used for this study. SPECT was performed over 4 h after individual or simultaneous injection of [(99m)Tc]TRODAT-1 (a dopamine transporter imaging agent) and [(123)I]ADAM (a serotonin transporter imaging agent). The results showed that the image quality and uptake ratios in different brain regions were comparable between single- and dual-isotope studies. The striatal [(99m)Tc]TRODAT-1 uptake in the PD monkey was markedly lower than that in normal monkeys. The uptake of [(123)I]ADAM in the midbrain of the PD monkey was comparable to that in the normal monkeys, but there were decreased uptakes in the thalamus and striatum of the PD monkey. Our results suggest that dual-isotope SPECT using [(99m)Tc]TRODAT-1 and [(123)I]ADAM can simultaneously evaluate changes in dopaminergic and serotonergic systems in a PD model.

Thallium-201 and I-123 Beta-Methyl Iodophenyl-Pentadecanoic Acid Dual Isotope Single Photon Emission Computed Tomography for Evaluating Reperfusion Injury After Successful Reperfusion Therapy

We report a reperfusion injury after rotational coronary atherectomy (RA) in a 66-year-old man with coronary artery disease. Submaximal exercise with thallium-201 single photon emission computed tomography (SPECT) imaging before reperfusion showed partially reversible perfusion defects in the apex and reversible perfusion defects in the anteroseptal area. Thallium-201 and I-123 beta-methyl iodophenyl-pentadecanoic acid (BMIPP) dual isotope SPECT was performed 5 days before and 1 hour after RA, and 1 month after RA. SPECT images at 1 hour after recovery of no reflow phenomenon after RA revealed enlargement of the defect sizes on thallium-201 and BMIPP uptakes in the anteroseptal area including the apex compared with those before RA. The defect size of thallium-201 uptake was progressively improved on 5 hour delayed redistribution imaging and 1 month after reperfusion compared with that of BMIPP uptake. In conclusion, the changes for the worse of thallium-201 uptake and fatty acid metabolism immediately after the no reflow phenomenon may indicate an injured membrane integrity with altered myocardial metabolism rather than myocardial ischemia. Thallium-201 and I-123 BMIPP dual isotope SPECT is useful for evaluating reperfusion injury after successful reperfusion therapy in a patient with acute coronary syndrome.

Simultaneous [99mTc]TRODAT-1 and [123I]ADAM Brain SPECT in Nonhuman Primates

This study examined the feasibility of simultaneous dopamine and serotonin transporter imaging using [(123)I]ADAM and [(99m)Tc]TRODAT-1 single photon emission computed tomography (SPECT). Simultaneous [(123)I]ADAM (185 MBq) and [(99m)Tc]TRODAT-1 (740 MBq) SPECT was performed in three age-matched female Formosan rock monkeys. An asymmetric energy window was used for dual, and symmetric energy windows were used for single-isotope imaging. Oral fluoxetine (20 mg) and intravenous methylphenidate HCl (1 mg/kg) were given 24 h and 10 min, respectively, before dual-isotope SPECT to test imaging specificities of [(123)I]ADAM and [(99m)Tc]TRODAT-1. Comparable image quality and uptake ratios between dual- and single-isotope SPECT scans were found. Dual-isotope SPECT in fluoxetine-pretreated monkeys showed decreased uptake of [(123)I]-ADAM, but not of [(99m)Tc]TRODAT-1. Dual-isotope SPECT in methylphenidate-pretreated monkeys showed decreased [(99m)Tc]TRODAT-1 uptake without affecting [(123)I]-ADAM uptake. Simultaneous [(123)I]-ADAM and [(99m)Tc]TRODAT-1 SPECT appears promising in nonhuman primates and may provide a suitable preclinical model with further clinical implications.

Ectopic Expression of the Sodium-Iodide Symporter Enables Imaging of Transplanted Cardiac Stem Cells In Vivo by Single-Photon Emission Computed Tomography or Positron Emission Tomography

We examined the sodium-iodide symporter (NIS), which promotes in vivo cellular uptake of technetium 99m ((99m)Tc) or iodine 124 ((124)I), as a reporter gene for cell tracking by single-photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging. Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo. The human NIS complementary deoxyribonucleic acid was transduced into rat cardiac-derived stem cells (rCDCs) using lentiviral vectors. Rats were injected intramyocardially with up to 4 million NIS(+)-rCDCs immediately after left anterior descending coronary artery ligation. Dual isotope SPECT (or PET) imaging was performed, using (99m)Tc (or (124)I) for cell detection and thallium 201 (or ammonia 13) for myocardial delineation. In a subset of animals, high resolution ex vivo SPECT scans of explanted hearts were obtained to confirm that in vivo signals were derived from the cell injection site. NIS expression in rCDCs did not affect cell viability and proliferation. NIS activity was verified in isolated transduced cells by measuring (99m)Tc uptake. NIS(+) rCDCs were visualized in vivo as regions of (99m)Tc or (124)I uptake within a perfusion deficit in the SPECT and PET images, respectively. Cells could be visualized by SPECT up to 6 days post-injection. Ex vivo SPECT confirmed that in vivo (99m)Tc signals were localized to the cell injection sites. Ectopic NIS expression allows noninvasive in vivo stem cell tracking in the myocardium, using either SPECT or PET. The general approach shows significant promise in tracking the fate of transplanted cells participating in cardiac regeneration, given its ability to observe living cells using clinically applicable imaging modalities.

Technetium-99m pyrophosphate/thallium-201 dual-isotope SPECT imaging predicts reperfusion injury in patients with acute myocardial infarction after reperfusion

Microcirculatory failure after reperfusion is clinically indicated to cause reperfusion injury whereas excessive intracellular calcium ion overload is experimentally proved as a key mechanism of reperfusion injury. We hypothesized that technetium-99m ((99m)Tc) pyrophosphate (Tc-PYP) uptake in injured but viable infarct-related myocardium with preserved myocardial perfusion after reperfusion estimated by thallium-201 ((201)Tl) uptake would be associated with final functional recovery. Dual-isotope Tc-PYP/(201)Tl single-photon emission computed tomography (SPECT) was performed 2 days after successful reperfusion therapy in patients with first acute myocardial infarction, and 50 patients (63 +/- 13 years old, female 22%) with preserved (201)Tl uptakes of > or = 50% in reperfused myocardium was followed for 1 month. Tc-PYP uptake was assessed as the heart-to-sternum (H/S) ratio. Two-dimensional echocardiography was also performed 2 days and 1 month after reperfusion to evaluate functional recovery. High Tc-PYP uptake, defined as the H/S ratio > or = 0.81, was predictive of chronic phase no functional recovery (73.7% in 14 of 19 patients with high uptake vs 16.1% in five of 31 patients without those, p < 0.0001). After adjustment for potential confounding variables, including electrocardiographic persistent ST segment elevation at 1 h after reperfusion, high Tc-PYP uptake remained independently predictive of no functional recovery with odds ratio of 8.7 (95% confidential interval = 2 to 38.7; p = 0.005). High Tc-PYP uptake in reperfused but viable infarct-related myocardium was a powerful predictor of no functional recovery, which may reflect excessive intracellular calcium ion overload caused by reperfusion injury. Tc-PYP/(201)Tl dual-isotope SPECT imaging can provide prognostic information after reperfusion.

Greater availability of dopamine transporters in patients with major depression — A dual-isotope SPECT study

In order to explore the neuropathology of the pre- and post-synaptic dopamine neurons of patients with major depression, we examined striatal D 2/D 3 receptor uptake and dopamine transporter (DAT) availability simultaneously in drug-free depressed patients using a dual-isotope single photon emission computed tomography (SPECT) imaging technique. Ten unmedicated patients with unmediated depression and ten healthy controls were recruited. The striatal dopamine D 2/D 3 receptor availability was measured using SPECT and [ 123I] IBZM, while DAT was measured using SPECT and [ 99mTc] TRODAT-1. The symptom changes of the drug-free patients were reassessed after a 4-week antidepressant treatment. DAT binding in the patient group were significantly higher than in control group. That was not the case, however, for striatal D 2/D 3 receptor availability. Pre-treatment striatal DAT availability correlated only marginally with changes in the Hamilton Depression Rating Scale after 4 weeks of treatment. Central dopamine functions may be altered in patients with major depression, particularly in the pre-synaptic sites.

Evaluation of No-Reflow Phenomenon Using 201TlCl/123I-BMIPP Dual-isotope Myocardial SPECT

We assessed the usefulness of (201)thallous chloride (TlCl)/(123)I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) dual-isotope single-photon emission computed tomography (SPECT) to identify the "no-reflow phenomenon," defined as inadequate myocardial perfusion through a given segment of the coronary circulation without angiographic evidence of mechanical vessel obstruction. (201)TlCl/(123)I-BMIPP SPECT was performed in 73 patients within approximately 1 week of initial acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). We divided the left ventricular myocardium into 17 segments on each SPECT image and scored tracer accumulation in each segment with a five-point scoring system according to the American Heart Association criteria. Total severity scores were calculated by summing the scores for all 17 segments. The mismatch ratio between myocardial perfusion and metabolism was derived from the (201)TlCl and (123)I-BMIPP total severity scores: mismatch ratio=((123)I-BMIPP total severity score -(201)TlCl total severity score)/(123)I-BMIPP total severity score. Patients were classified according to Thrombolysis in Myocardial Infarction (TIMI) flow grade as having TIMI reflow grade 0-I (TIMI 0-I reflow group; n=11), II (TIMI II reflow group; n=17) and III (TIMI III reflow group; n=45). The TIMI III reflow group was subdivided into two groups with (201)TlCl total severity scores of < or =13 (TIMI III (A) reflow group; n=36) and > or =14 (TIMI III (B) reflow group; n=9), respectively. The mismatch ratios in the TIMI II (0.4 +/- 0.3) and TIMI III (0.4 +/- 0.2) reflow groups were significantly higher than that in the TIMI 0-1 reflow group (0.1 +/- 0.1, p<0.05). Although coronary angiography revealed TIMI III flow after reperfusion, the mismatch ratios in the TIMI III (B) reflow group (0.2 +/- 0.1) and in the TIMI 0-I reflow group (0.1 +/- 0.1) were significantly lower than that in the TIMI III (A) reflow group (0.4 +/- 0.2, p<0.01), reflecting noneffective recanalization (so called no-reflow phenomenon). (201)TlCl/(123)I-BMIPP dual-isotope myocardial SPECT reveals the biochemical degree of the no-reflow phenomenon, whereas coronary angiography shows recanalized vascular flow only. Dual-isotope myocardial SPECT might be useful for evaluating reperfusion therapy.