Dataset Information

Quantification of intramyocardial blood volume with 99mTc-RBC SPECT-CT imaging: A preclinical study.

ABSTRACT: BACKGROUND:Currently, there is no established non-invasive imaging approach to directly evaluate myocardial microcirculatory function in order to diagnose microvascular disease independent of co-existing epicardial disease. In this work, we developed a methodological framework for quantification of intramyocardial blood volume (IMBV) as a novel index of microcirculatory function with SPECT/CT imaging of 99mTc-labeled red blood cells (RBCs). METHODS:Dual-gated myocardial SPECT/CT equilibrium imaging of 99mTc-RBCs was performed on twelve canines under resting conditions. Five correction schemes were studied: cardiac gating with no other corrections (CG), CG with attenuation correction (CG + AC), CG + AC with scatter correction (CG + AC + SC), dual cardiorespiratory gating with AC + SC (DG + AC + SC), and DG + AC + SC with partial volume correction (DG + AC + SC + PVC). Quantification of IMBV using each approach was evaluated in comparison to those obtained from all corrections. The in vivo SPECT estimates of IMBV values were validated against those obtained from ex vivo microCT imaging of the casted hearts. RESULTS:The estimated IMBV with all corrections was 0.15 ± 0.03 for the end-diastolic phase and 0.11 ± 0.03 for the end-systolic phase. The cycle-dependent change in IMBV (?IMBV) with all corrections was 23.9 ± 8.6%. Schemes that applied no correction or partial correction resulted in significant over-estimation of IMBV and significant under-underestimation of ?IMBV. Estimates of IMBV and ?IMBV using all corrections were consistent with values reported in the literature using invasive techniques. In vivo SPECT estimates of IMBV strongly correlated (R2 ? 0.70) with ex vivo measures for the various correction schemes, while the fully corrected scheme yielded the smallest bias. CONCLUSIONS:Non-invasive quantification of IMBV is feasible using 99mTc-RBCs SPECT/CT imaging, however, requires full compensation of physical degradation factors.

SUBMITTER: Mohy-Ud-Din H

PROVIDER: S-EPMC5985225 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Quantification of intramyocardial blood volume with <sup>99m</sup>Tc-RBC SPECT-CT imaging: A preclinical study.

Mohy-Ud-Din Hassan H Boutagy Nabil E NE Stendahl John C JC Zhuang Zhen W ZW Sinusas Albert J AJ Liu Chi C

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 20170710 6

<h4>Background</h4>Currently, there is no established non-invasive imaging approach to directly evaluate myocardial microcirculatory function in order to diagnose microvascular disease independent of co-existing epicardial disease. In this work, we developed a methodological framework for quantification of intramyocardial blood volume (IMBV) as a novel index of microcirculatory function with SPECT/CT imaging of <sup>99m</sup>Tc-labeled red blood cells (RBCs).<h4>Methods</h4>Dual-gated myocardial ...[more]

PMID: 28695406

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Project description:ObjectiveSPECT/CT with 99mTc-macroaggregated albumin (MAA) is generally used for diagnostic work-up prior to transarterial radioembolization (TARE) to exclude shunts and to provide additional information for treatment stratification and dose calculation. C-arm CT is used for determination of lobular vascular supply and assessment of parenchymal blood volume (PBV). Aim of this study was to correlate MAA-uptake and PBV-maps in hepatocellular carcinoma (HCC) and hepatic metastases of the colorectal carcinoma (CRC).Materials and methods34 patients underwent a PBV C-arm CT immediately followed by 99mTc-MAA injection and a SPECT/CT acquisition after 1 h uptake. MAA-uptake and PBV-maps were visually assessed and semi-quantitatively analyzed (MAA-tumor/liver-parenchyma = MAA-TBR or PBV in ml/100ml). In case of a poor match, tumors were additionally correlated with post-TARE 90Y-Bremsstrahlung-SPECT/CT as a reference.Results102 HCC or CRC metastases were analyzed. HCC presented with significantly higher MAA-TBR (7.6 vs. 3.9, p<0.05) compared to CRC. Tumors showed strong intra- and inter-individual dissimilarities between TBR and PBV with a weak correlations for capsular HCCs (r = 0.45, p<0.05) and no correlation for CRC. The demarcation of lesions was slightly better for both HCC and CRC in PBV-maps compared to MAA-SPECT/CT (exact match: 52%/50%; same intensity/homogeneity: 38%/39%; insufficient 10%/11%). MAA-SPECT/CT revealed a better visual correlation with post-therapeutic 90Y-Bremsstrahlung-SPECT/CT.ConclusionThe acquisition of PBV can improve the detectability of small intrahepatic tumors and correlates with the MAA-Uptake in HCC. The results indicate that 99mTc-MAA-SPECT/CT remains to be the superior method for the prediction of post-therapeutic 90Y-particle distribution, especially in CRC. However, intra-procedural PBV acquisition has the potential to become an additional factor for TARE planning, in addition to improving the determination of segment and tumor blood supply, which has been demonstrated previously.

Project description:For brown adipose tissue (BAT) to be effective at consuming calories, its blood flow must increase enough to provide sufficient fuel to sustain energy expenditure and also transfer the heat created to avoid thermal injury. Here we used a combination of human and rodent models to assess changes in BAT blood flow and glucose utilization.(99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT (n = 7) and SPECT/CT (n = 74) scans done in adult humans for parathyroid imaging were reviewed for uptake in regions consistent with human BAT. Site-directed biopsies of subcutaneous and deep neck fat were obtained for electron microscopy and gene expression profiling. In mice, tissue perfusion was measured with (99m)Tc-MIBI (n = 16) and glucose uptake with (18)F-FDG (n = 16). Animals were kept fasting overnight, anesthetized with pentobarbital, and given intraperitoneally either the ?3-adrenergic receptor agonist CL-316,243, 1 mg/kg (n = 8), or saline (n = 8) followed by radiotracer injection 5 min later. After 120 min, the mice were imaged using SPECT/CT or PET/CT. Vital signs were recorded over 30 min during the imaging. BAT, white adipose tissue (WAT), muscle, liver, and heart were resected, and tissue uptake of both (99m)Tc-MIBI and (18)F-FDG was quantified by percentage injected dose per gram of tissue and normalized to total body weight.In 5.4% of patients (4/74), (99m)Tc-MIBI SPECT/CT showed increased retention in cervical and supraclavicular fat that displayed multilocular lipid droplets, dense capillary investment, and a high concentration of ovoid mitochondria. Expression levels of the tissue-specific uncoupling protein-1 were 180 times higher in BAT than in subcutaneous WAT (P < 0.001). In mice, BAT tissue perfusion increased by 61% (P < 0.01), with no significant changes in blood flow to WAT, muscle, heart, or liver. CL-316,243 increased glucose uptake in BAT even more, by 440% (P < 0.01).Pharmacologic activation of BAT requires increased blood flow to deliver glucose and oxygen for thermogenesis. However, the glucose consumption far exceeds the vascular response. These findings demonstrate that activated BAT increases glucose uptake beyond what might occur by increased blood flow alone and suggest that activated BAT likely uses glucose for nonthermogenic purposes.

Project description:A well-established approach for diagnostic imaging of osteomyelitis (OM), a bone infection, is simultaneous SPECT-CT of 99mTc sulfur colloid (SC) and 111In white blood cells (WBC). This method provides essentially perfect spatial registration of the tracers within anatomic sites of interest. Currently, diagnosis is based purely on a visual assessment-where relative discordance between 99mTc and 111In uptake in bone, i.e., high 111In and low 99mTc, suggests OM. To achieve more quantitative images, noise, scatter, and crosstalk between radionuclides must be addressed through reconstruction. Here the authors compare their Monte Carlo-based joint OSEM (MC-JOSEM) algorithm, which reconstructs both radionuclides simultaneously, to a more conventional triple-energy window-based reconstruction (TEW-OSEM), and to iterative reconstruction with no compensation for scatter (NC-OSEM).The authors created numerical phantoms of the foot and torso. Multiple bone-infection sites were modeled using high-count Monte Carlo simulation. Counts per voxel were then scaled to values appropriate for 111In WBC and 99mTc SC imaging. Ten independent noisy projection image sets were generated by drawing random Poisson deviates from these very low-noise images. Data were reconstructed using the two iterative scatter-compensation methods, TEW-OSEM and MC-JOSEM, as well as the uncorrected method (NC-OSEM). Mean counts in volumes of interest (VOIs) were used to evaluate the bias and precision of each method. Data were also acquired using a phantom, approximately the size of an adult ankle, consisting of regions representing infected and normal bone marrow, within a bone-like attenuator and surrounding soft tissue; each compartment contained a mixture of 111In and 99mTc. Low-noise data were acquired during multiple short scans over 29 h on a Siemens Symbia T6 SPECT-CT with medium-energy collimators. Pure 99mTc and 111In projection datasets were derived by fitting the acquired projections to the sum of 99mTc and 111In contributions, using the known half-lives. Uncontaminated data were scaled and recombined into six datasets with different activity ratios; ten Poisson noise realizations were then generated for each ratio. VOIs in each of the compartments were used to evaluate the bias and precision of each method with respect to reconstructions of uncontaminated datasets. In addition to the simulated and acquired phantom images, the authors reconstructed patient images with MC-JOSEM and TEW-OSEM. Patient reconstructions were assessed qualitatively for lesion contrast, spatial definition, and scatter.For all simulated and acquired infection phantoms, the root-mean squared-error of measured 99mTc activity was significantly improved with MC-JOSEM and TEW-OSEM in comparison to NC-OSEM reconstructions. While MC-JOSEM trended toward outperforming TEW-OSEM, the improvement was only found to be significant (p<0.001) for the acquired bone phantom in which a wide range of 111In∕99mTc concentration ratios were tested. In all cases, scatter correction did not significantly improve 111In quantitation.Compensation for scatter and crosstalk is useful for improving quality, bias, and precision of 99mTc activity estimates in simultaneous dual-radionuclide imaging of OM. The use of the more rigorous MC-based estimates provided marginal improvements over TEW. While the phantom results were encouraging, more subjects are needed to evaluate the usefulness of quantitative 111In∕99mTc SPECT-CT in the clinic.

Project description:Authors' goal is to evaluate the performance of simultaneous (99m)Tc-MDP/(123)I-MIBG tumor imaging with fast Monte-Carlo (MC) based joint iterative reconstruction as compared to sequential (99m)Tc-MDP and (123)I-MIBG tumor imaging.Noise-free (99m)Tc and (123)I SPECT projections were acquired separately using an anthropomorphic torso phantom modified to include a fillable tube around the lungs to mimic ribs. Additionally, (99m)Tc and (123)I projections were acquired separately using a 1-cm spherical "tumor" placed at various distances from one detector. Tumor-present data were generated by adding tumor projections to the torso phantom data, which were scaled to the total counts in typical clinical studies. Twenty-five noise realizations were generated by adding Poisson noise to the projection data for each radionuclide. Dual-radionuclide data were synthesized by summing the (99m)Tc and (123)I projections. Image reconstruction was performed using: (1) SR-OSEM, ordered subset expectation maximization (OSEM) without scatter correction (SC) using single-radionuclide (SR) data; (2) SR-MC-OSEM, OSEM with a fast MC-based SC using SR data; (3) DR-OSEM, OSEM without SC using dual-radionuclide (DR) data; and (4) DR-MC-JOSEM, joint OSEM with a fast MC-based SC using DR data. Ten (99m)Tc-MDP and ten (123)I-MIBG data sets, which had tumors mathematically inserted, were also used to evaluate the performance of authors' approach. For the phantom study, relative bias and relative standard deviation of tumor uptake were computed for each tumor using the tumor uptake in the noise-free single-radionuclide images, which were reconstructed by SR-MC-OSEM, as the gold standard. For both the phantom and constructed patient studies, mean contrast and standard deviation of contrast were computed for each tumor for both the single- and dual-radionuclide images. Additionally, contrast recovery was computed as the ratio between mean contrast and the mean contrast for SR-MC-OSEM.For the phantom study, DR-MC-JOSEM yielded 2.7% on average relative bias of tumor uptake using the images, which were reconstructed from the noise-free SR data with SR-MC-OSEM, as the gold-standard. For both the phantom and constructed patient studies, DR-MC-JOSEM yielded 94.7% and 95.2% tumor contrast recovery on average using SR-MC-OSEM as the reference, in the phantom and constructed patient studies, respectively. DR-MC-JOSEM yielded comparable relative standard deviation of bias and standard deviation of contrast to SR-MC-OSEM.Simultaneous (99m)Tc-MDP/(123)I-MIBG tumor imaging using authors' dual-radionuclide reconstruction approach yielded comparable image quality to sequential (99m)Tc-MDP and (123)I-MIBG imaging. For patients who need to undergo both scans, authors' approach offers perfectly registered dual-tracer images under identical conditions without compromising image quality, and reduces the imaging cost while increasing patient throughput.

Project description:BACKGROUND:Sensitive and specific detection of nodal status, sites of metastases and low-volume recurrent disease could greatly improve management of patients with advanced prostate cancer. Prostate-specific membrane antigen (PSMA) is a well-established marker for prostate carcinoma with increased levels of expression in high-grade, hormone-refractory and metastatic disease. The monoclonal antibody (mAb) J591 is directed against an extracellular epitope of PSMA and has been shown to efficiently target disseminated disease including metastases in lymph nodes and bone. Its use as a diagnostic imaging agent however is limited due to its slow pharmacokinetics. In this study a diabody derived from mAb J591 was developed as a single photon emission computed tomography (SPECT) tracer with improved pharmacokinetics for the detection of PSMA expression in prostate cancer. METHODS:A diabody in VH-VL orientation and with a C-terminal cysteine was expressed in HEK293T cells and purified by a combination of metal ion affinity and size exclusion chromatography. Specificity and affinity were determined in cell binding studies. For SPECT imaging, the diabody was site-specifically labelled with [99mTc(CO)3]+ via the C-terminal His tag and evaluated in a subcutaneous DU145/DU145-PSMA prostate carcinoma xenograft model. RESULTS:J591C diabody binds to PSMA-expressing cells with low nanomolar affinity (3.3?±?0.2 nM). SPECT studies allowed imaging of tumour xenografts with high contrast from 4 h post injection (p.i.). Ex vivo biodistribution studies showed peak tumour uptake of the tracer of 12.1%?±?1.7% injected dose (ID)/g at 8 h p.i. with a tumour to blood ratio of 8.0. Uptake in PSMA-negative tumours was significantly lower with 6.3%?±?0.5% at 8 h p.i. (p?<?0.001). CONCLUSION:The presented diabody has favourable properties required to warrant its further development for antibody-based imaging of PSMA expression in prostate cancer, including PSMA-specific uptake, favourable pharmacokinetics compared to the parental antibody and efficient site-specific radiolabelling with 99mTc.

Project description:BACKGROUND:The aim of this study was to evaluate the diagnostic efficacy of 18F-fluorocholine (18F-FCH) PET/CT for uremic hyperparathyroidism (uHPT) compared to 99mTc-sestaMIBI SPECT/CT and ultrasonography (US). METHODS:A total of 17 uHPT patients with stage 5 chronic kidney disease (CKD) were prospectively enrolled. All patients underwent US, 99mTc-sestaMIBI SPECT/CT, and 18F-FCH within 2?months and received surgical treatment. Visual and quantitative methods were used for image analyses. Intraoperative localization and postoperative histological results of the reference standard as well as the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the three modalities were analyzed using Pearson's ?2 tests. In addition, the diagnostic efficacy of 18F-FCH PET/CT for uHPT was evaluated. The relationships between PET parameters and laboratory parameters were assessed using the Spearman correlation coefficient. RESULTS:A total of 63 parathyroid hyperplasia lesions were resected in 17 uHPT patients, and 53 lesions were detected using 18F-FCH PET/CT with no false-positive results. The sensitivity, specificity, accuracy, PPV, and NPV were 84.13%, 100%, 86.49%, 100%, and 52.38%, respectively. In comparison, the corresponding values for 99mTc-sestaMIBI SPECT/CT and US were 63.49%, 90.91%, 67.57%, 97.56%, and 30.30% and 61.90%, 81.82%, 64.86%, 95.12%, and 27.27%, respectively. The volume of hyper-functioning parathyroid glands was significantly different between lesions positive in 18F-FCH PET/CT and negative in 18F-FCH PET/CT (mean volume 1.36 ± 0.55?cm3 vs. 0.83 ± 0.26?cm3; P = 0.019). US misidentified intrathyroidal parathyroid hyperplasia as thyroid nodules in three patients, while 18F-FCH PET correctly identified the anatomy. No significant associations were observed between PET parameters and laboratory parameters in uHPT. CONCLUSION:18F-FCH PET/CT was more sensitive and accurate for uHPT than 99mTc-sestaMIBI SPECT/CT and US, and had better preoperative diagnostic efficacy, particularly for lesions diagnosed as a thyroid nodule by US.

Dataset Information

Quantification of intramyocardial blood volume with 99mTc-RBC SPECT-CT imaging: A preclinical study.

Publications

Quantification of intramyocardial blood volume with <sup>99m</sup>Tc-RBC SPECT-CT imaging: A preclinical study.

Similar Datasets

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