Attenuation correction for rotating multi-segment slant-hole SPECT in breast imaging

Rotating multi-segment slant-hole (RMSSH) SPECT is suitable for detecting small and low-contrast breast lesions since it has much higher detection efficiency compared with parallel-hole SPECT for the same resolution and can image the breast at a closer distance.Our RMSSH SPECT image reconstruction extends a previous rotation-shear transformation based 3D iterative reconstruction method to include non-uniform attenuation compensation. Reconstructed RMSSH SPECT images with attenuation compensation show much improved quantitative accuracy and less image artifacts than without. We conclude that attenuation compensation provides RMSSH SPECT images with improved quality and quantitative accuracy.     

Recent developments in 99mTc and 123I-radiopharmaceuticals for SPECT imaging

Availability of ¹²³I of high radionuclidic purity has encouraged the development of ¹²³I-based radiopharmaceuticals for the assessment of myocardial fatty acid metabolism, myocardial neuronal activity, and for receptor and antibody imaging. Advances in the chemistry of technetium have resulted in the development of novel agents for myocardial and cerebral perfusion and renal function studies. Monoclonal antibodies labeled with ^99mTc show promise for imaging neoplastic lesions, myocardial infarcts, and thrombus localization. Recent developments in ¹²³I and ^99mTc agents for myocardial and brain imaging studies are discussed.     

Nonlinear Dual Reconstruction of SPECT Activity and Attenuation Images

In single photon emission computed tomography (SPECT), accurate attenuation maps are needed to perform essential attenuation compensation for high quality radioactivity estimation. Formulating the SPECT activity and attenuation reconstruction tasks as coupled signal estimation and system parameter identification problems, where the activity distribution and the attenuation parameter are treated as random variables with known prior statistics, we present a nonlinear dual reconstruction scheme based on the unscented Kalman filtering (UKF) principles. In this effort, the dynamic changes of the organ radioactivity distribution are described through state space evolution equations, while the photon-counting SPECT projection data are measured through the observation equations. Activity distribution is then estimated with sub-optimal fixed attenuation parameters, followed by attenuation map reconstruction given these activity estimates. Such coupled estimation processes are iteratively repeated as necessary until convergence. The results obtained from Monte Carlo simulated data, physical phantom, and real SPECT scans demonstrate the improved performance of the proposed method both from visual inspection of the images and a quantitative evaluation, compared to the widely used EM-ML algorithms. The dual estimation framework has the potential to be useful for estimating the attenuation map from emission data only and thus benefit the radioactivity reconstruction.     

Development of SPECT imaging agents for the norepinephrine transporters: [123I]INER

A series of reboxetine analogs was synthesized and evaluated for in vitro binding as racemic mixtures. The best candidate (INER) was synthesized as the optically pure (S,S) enantiomer, labeled with iodine-123 and its in vivo binding determined by SPECT imaging in baboons. The in vivo specificity, selectivity, and kinetics of [123I]INER make it a promising agent for imaging NET in vivo by noninvasive SPECT imaging.     

Synthesis and characterization of 123I-CMICE-013: A potential SPECT myocardial perfusion imaging agent

Coronary artery disease (CAD) is a major cause of death in Canada and the United States. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a useful diagnostic test in the management of patients with CAD. The widely used SPECT MPI agents, ^99mTc sestamibi and ^99mTc tetrofosmin, exhibit less than ideal pharmacokinetic properties with decreasing uptake with higher flows. ¹²³I has a similar energy as ^99mTc, an ideal half life, and is readily available from cyclotrons. The objective of this study was to develop an ¹²³I labeled MPI agent based on rotenone, a mitochondrial complex I inhibitor, as an alternative to currently available SPECT MPI agents. Methods: ¹²³I-CMICE-013 was synthesized by radiolabeling rotenone with ¹²³I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60 °C for 45 min, followed by RP-HPLC purification. The product was formulated in 5% EtOH in 10 mM NaOAc pH 6.5. The inactive analog ¹²⁷I-CMICE-013 was isolated and characterized by NMR and mass spectrometry, and the structure determined. Micro-SPECT imaging studies were carried out in normal and infarcted rats. Biodistribution studies were performed in normal rats at 2 h (n = 6) and 24 h (n = 8) post injection (p.i.). Results: ¹²³I-CMICE-013 was isolated with >95% radiochemical purity and high specific activity (14.8–111 GBq/μmol; 400–3000 mCi/μmol). Structural analysis showed that rotenone was iodinated at 7′-position, with removal of the 6′,7′-double bond, and addition of a hydroxy group at 6′-position. MicroSPECT images in normal rats demonstrated homogeneous and sustained myocardial uptake with minimal interference from lung and liver. Absent myocardial perfusion was clearly identified in rats with permanent left coronary artery ligation and ischemia-reperfusion injury. In vivo biodistribution studies in normal rats at 2 h p.i. showed significant myocardial uptake (2.01 ± 0.48%ID/g) and high heart to liver (2.98 ± 0.93), heart to lung (4.11 ± 1.04) and heart to blood (8.37 ± 3.97) ratios. At 24 h p.i., the majority of ¹²³I-CMICE-013 was cleared from tissues, and a significant amount of tracer was found in the thyroid, indicating in vivo deiodination of the tracer. Conclusion: ¹²³I-CMICE-013 is a promising new radiotracer for SPECT MPI with high myocardial uptake, very good target to background ratios and favorable biodistribution characteristics.     

An APD-based iterative reconstruction method for simultaneous technetium-99m/iodine-123 SPECT imaging

Dual-isotope SPECT (DI-SPECT) studies offer significant advantages over sequential scans, foremost among them faster acquisition and perfect image registration. However, reconstructed images may be affected by substantial cross-talk contamination rendering them inadequate for diagnosis. This effect is especially strong for isotopes with close photopeak energies, such as ^99mTc (140 keV) and ¹²³I (159 keV). In this paper we present an iterative DI-SPECT reconstruction method which includes accurate, analytically computed scatter corrections provided by the APD (analytical photon distribution) algorithm. This algorithm calculates first and second order Compton scatter (based on the Klein–Nishina formula) and first order Rayleigh scatter. Both self-scatter and cross-talk between the two isotopes are evaluated using patient specific attenuation maps and an initial activity distribution estimate. To validate our method we performed experiments using the Data Spectrum, Inc. thorax phantom and a SPECT/CT camera system. Reconstructed images demonstrate significant improvement in data quantitation. Their quantitative accuracy increases up to a factor of two, even for activity ratios which strongly enhance cross-talk effects and seriously degrade projections.     

Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates

The pharmacokinetics of [¹²³I]iomazenil (Ro 16-0154) in 5 healthy human volunteers were compared to those in 2 hypothermic and 3 normothermic anesthetized monkeys. Following intravenous injection in humans and monkeys, [¹²³I]iomazenil rapidly diffused outside the vascular bed and was cleared from the arterial plasma triexponentially. The clearance half-times in hypothermic animals were protracted to values closer to those of the human. [¹²³I]lomazenil was metabolized mainly to a polar radiometabolite (not extracted by ethyl acetate) in the human whereas an additional lipophilic radiometabolite was detected in the monkey. In vitro and in vivo studies showed that [¹²³I]Iomazenil established equal concentrations in association with the cellular and plasma component of the blood, indicating that the plasma clearance of [¹²³I]iomazenil mirrors that of the blood. Analysis of organs from a monkey given [¹²³I]iomazenil showed that the parent compound was actively taken up by peripheral organs; the polar radiometabolite accumulated mainly in the bile and the kidneys whereas the non-polar radiometabolite accumulated in the urine and kidneys. Greater than 90% of the radioactivity in the different regions of the brain was unchanged parent [¹²³I]iomazenil.     

Clinical Comparison of 99mTc Exametazime and 123I Ioflupane SPECT in Patients with Chronic Mild Traumatic Brain Injury

Background

This study evaluated the clinical interpretations of single photon emission computed tomography (SPECT) using a cerebral blood flow and a dopamine transporter tracer in patients with chronic mild traumatic brain injury (TBI). The goal was to determine how these two different scan might be used and compared to each other in this patient population.

Methods and Findings

Twenty-five patients with persistent symptoms after a mild TBI underwent SPECT with both ^99mTc exametazime to measure cerebral blood flow (CBF) and ¹²³I ioflupane to measure dopamine transporter (DAT) binding. The scans were interpreted by two expert readers blinded to any case information and were assessed for abnormal findings in comparison to 10 controls for each type of scan. Qualitative CBF scores for each cortical and subcortical region along with DAT binding scores for the striatum were compared to each other across subjects and to controls. In addition, symptoms were compared to brain scan findings. TBI patients had an average of 6 brain regions with abnormal perfusion compared to controls who had an average of 2 abnormal regions (p<0.001). Patient with headaches had lower CBF in the right frontal lobe, and higher CBF in the left parietal lobe compared to patients without headaches. Lower CBF in the right temporal lobe correlated with poorer reported physical health. Higher DAT binding was associated with more depressive symptoms and overall poorer reported mental health. There was no clear association between CBF and DAT binding in these patients.

Conclusions

Overall, both scans detected abnormalities in brain function, but appear to reflect different types of physiological processes associated with chronic mild TBI symptoms. Both types of scans might have distinct uses in the evaluation of chronic TBI patients depending on the clinical scenario.     

Characterization of the four isomers of 123I-CMICE-013: A potential SPECT myocardial perfusion imaging agent

Myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) is widely used in the assessment of coronary artery disease (CAD). We have developed ¹²³I-CMICE-013 based on rotenone, a mitochondrial complex I (MC-1) inhibitor, as a promising new MPI agent. Our synthesis results in a mixture of four species of ¹²³I-CMICE-013 A, B, C, D. In this study, we separated the four species and evaluated their biodistribution and imaging properties. The cold analogs ¹²⁷I-CMICE-013 A, B, C, D were isolated and characterized and their chemical structures proposed. Methods: ¹²³I-CMICE-013 was synthesized by radiolabeling rotenone with Na¹²³I in trifluoroacetic acid (TFA) with iodogen as the oxidizing agent at 60 °C for 45 min, and the four species were separated by RP-HPLC. The cold analogs ¹²⁷I-CMICE-013 A, B, C and D were isolated with a similar procedure and characterized by NMR and mass spectrometry. Biodistribution and microSPECT imaging studies were carried out on normal rats. Results: We propose the mechanism of the rotenone iodination and the structures of the four species. First, I⁺ forms an intermediate three-membered ring with 6′ and 7′ carbons. Second, the lone electron pair of the water molecule attacks the 6′ or 7′-carbon, following by the formation of 6′-OH, and 7′-I bonds as in major products C and D, or 6′-I and 7′-OH bonds as in minor products A and B. The weaker 6′-I bond in the intermediate prompts the nucleophilic attachment of water at the favorable 6′-carbon to generate C and D. MicroSPECT images of ¹²³I-CMICE-013 A, B, C, D in rats showed clear visualization of myocardium and little interference from lung and liver. The imaging time activity curves and biodistribution data showed complex profiles for the four isomers, which is not expected from the structure activity relationship theory. Conclusion: ^123/127I-CMICE-013 A and B are constitutional isomers with C and D, while A and C are diastereomers of B and D, respectively. Overall, the biological characteristics of the four species are not correlated perfectly with their molecular structures.     

Simultaneous dual-isotope 123I/99mTc acquisition using CZT-based cameras: Toward a one-stop-shop SPECT in heart failure patients

The CZT-cameras (DNM 530c and DSPECT) have only recently been introduced, and the impact of the increased energy resolution remains unknown. This paper summarizes the evidence on the assessment of: (i) the left ventricular function, (ii) the ¹²³I/^99mTc mismatch, and (iii) the heart-to-mediastinum ratio (HMR) of ¹²³I-metaiodobenzylguanidine (MIBG) uptake under dual-isotope conditions (^99mTc and ¹²³I) using cadmium-zinc-telluride (CZT) technology. The diagnostic accuracy of CZT cameras for myocardial sympathetic innervation imaging, left ventricular function and perfusion assessment using perfusion-gated SPECT have only been established in a few studies, under single-isotope conditions. Limited evidence is available regarding simultaneous dual-isotope acquisition using CZT-cameras. However, recently reported data have shown that CZT cameras allow, in dual-isotope (¹²³I and ^99mTc) acquisitions and under routine conditions: (i) a simultaneous and accurate segmental study of myocardial innervation and perfusion (match and mismatch), (ii) the ventricular function assessment (EDV, ESV and LVEF), and (iii) the determination of the late HMR of cardiac ¹²³I-MIBG uptake in patients with heart failure. However, this latter should be performed using transaxial reconstructed images and a linear correction based on phantom data acquisitions.

The effect of scatter correction and radius of rotation on semiquantitative measurements in SPECT 123I-FP-CIT imaging. A phantom study

PurposeThe high energy emissions of ¹²³I and the suboptimal radius of rotation affect the semiquantitative measurements performed during ¹²³I-FP-CIT tomographic imaging. An in-house extra low cost striatum phantom with brain and striatum compartments was constructed and was used to study the effects of Triple Energy Window scatter correction (TEW-SC) and radius of rotation on the Specific Binding Ratio (SBR) measurements.Materials and methodsThe phantom compartments were filled with radioactive ¹²³I solutions with varying concentrations, in a series of experiments. Tomographic images were acquired at six different radii of rotation, with and without TEW-SC and the SBRs were calculated using appropriate regions of interest, as in clinical imaging.ResultsSBRs decreased with increasing radius of rotation in both non-SC and TEW-SC images, the decrease being more pronounced in the latter. The application of TEW-SC increases SBR values by 40% on average. A maximum %Recovery of 42.7% of the true SBR value was achieved in the non-SC images, which increased to 64.6% after TEW-SC. Appropriate correction factors (CF) were calculated in order to make the SBR values independent on the radius of rotation, which could be used to correct SBR values obtained from tomographic acquisitions with suboptimal radius of rotation.ConclusionThe use of appropriate CF can provide more consistent SBR values and a more meaningful comparison between SBRs calculated from images acquired at different radii of rotation.     

Sensitivity and Specificity of Dual-Isotope 99mTc-Tetrofosmin and 123I Sodium Iodide Single Photon Emission Computed Tomography (SPECT) in Hyperparathyroidism

Purpose

Despite recommendations for ^99mTc-tetrofosmin dual tracer imaging for hyperparathyroidism in current guidelines, no report was published on dual-isotope ^99mTc-tetrofosmin and ¹²³I sodium iodide single-photon-emission-computed-tomography (SPECT). We evaluated diagnostic accuracy and the impact of preoperative SPECT on the surgical procedures and disease outcomes.

Methods

Analysis of 70 consecutive patients with primary hyperparathyroidism and 20 consecutive patients with tertiary hyperparathyroidism. Imaging findings were correlated with surgical results. Concomitant thyroid disease, pre- and postoperative laboratory measurements, histopathological results, type and duration of surgery were assessed.

Results

In primary hyperparathyroidism, SPECT had a sensitivity of 80% and a positive predictive value of 93% in patient-based analysis. Specificity was 99% in lesion-based analysis. Patients with positive SPECT elicit higher levels of parathyroid hormone and higher weight of resected parathyroids than SPECT-negative patients. Duration of parathyroid surgery was on average, approximately 40 minutes shorter in SPECT-positive than in SPECT-negative patients (89±46 vs. 129±41 minutes, p=0.006); 86% of SPECT-positive and 50% of SPECT-negative patients had minimal invasive surgery (p = 0.021). SPECT had lower sensitivity (60%) in patients with tertiary hyperparathyroidism; however, 90% of these patients had multiple lesions and all of these patients had bilateral lesions.

Conclusion

Dual-isotope SPECT with ^99mTc-tetrofosmin and ¹²³I sodium iodide has a high diagnostic value in patients with primary hyperparathyroidism and allows for saving of operation time. Higher levels of parathyroid hormone and higher glandular weight facilitated detection of parathyroid lesion. Diagnostic accuracy of preoperative imaging was lower in patients with tertiary hyperparathyroidism.