Dynamic SPECT Research Articles

Application value of dynamic SPECT 99Tcm-GSA scintigraphy assessing regional liver function changes before and after portal vein embolization

Objective To investigate the application value of dynamic single-photon emission computed tomography (SPECT) 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection (99Tcm-GSA) scintigraphy assessing regional liver function changes before and after portal vein embolization (PVE). Methods The retrospective cross-sectional study was conducted. The clinical data of 11 patients with Bismuth Ⅲa hilar cholangiocarcinoma who were admitted to the General Hospital of People′s Liberation Army (10 patients) and Beijing Tsinghua Changgung Hospital (1 patient) from October 2010 to October 2016 were collected. B ultrasound-guided percutaneous transhepatic ipsilateral exbolization was performed before radical resection of hilar cholangiocarcinoma. Dynamic SPECT 99Tcm-GSA scintigraphy was performed to calculate and compare the changes of functional liver volume (FLV), morphological liver volume (MLV) and functional liver density (FLD) in embolized lobe and non-embolized lobe before PVE and 2 weeks after PVE. Observation indicators: (1) the changes of serum indexes in 2 weeks before and after PVE; (2) the changes of FLV, MLV and FLD in the whole liver, embolized and non-embolized lobes in 2 weeks before and after PVE; (3) surgical and postoperative situations of hilar cholangiocarcinoma; (4) follow-up and survival situations. Follow-up using outpatient examination and telephone interview was performed to detect postoperative serum toal bilirubin (TBil) level, with or without peritoneal effusion and survival up to June 2017. Measurement data with normal distribution were represented as ±s. The comparisons of pre-and post-operative data were analyzed by the paired t test. Results (1) The changes of serum indexes in 2 weeks before and after PVE: 11 patients underwent successful right PVE. The alanine aminotransferase (ALT), TBil, albumin (Alb), Platelets (PLT) and prothrombin time (PT) were respectively (113±20)U/L, (73±8)μmol/L, (35.0±2.5)g/L, (209±58)×109/L, (11.4±0.7)seconds in 2 weeks before PVE and (120±18)U/L, (36±7)μmol/L, (34.4±3.2)g/L, (224±82)×109/L, (11.2±0.8)seconds in 2 weeks after PVE, with a statistically significant difference in TBil level (t=-10.592, P 0.05). (2) The changes of FLV, MLV and FLD in the whole liver, embolized and non-embolized lobes in 2 weeks before and after PVE: the FLV, MLV and FLD of the whole liver were respectively (894±255)mL, (1 552±504)mL, 0.59±0.14 in 2 weeks before PVE and (812±206)mL, (1 521±422)mL, 0.55±0.16 in 2 weeks after PVE, with no statistically significant difference (t=1.569, 0.666, 1.980, P>0.05). The FLV, MLV and FLD of the embolized lobe were respectively (623±275)mL, (1 047±394)mL, 0.62±0.14 in 2 weeks before PVE and (375±240)mL, (865±337)mL, 0.44±0.24 in 2 weeks after PVE, with statistically significant differences (t=5.909, 3.736, 3.359, P<0.05); the descending percentages were respectively 38.1%, 9.8% and 24.6%. The FLV, MLV and FLD of the non-embolized lobe were respectively (274±152)mL, (530±176)mL, 0.52±0.21 in 2 weeks before PVE and (436±149)mL, (656±133)mL, 0.68±0.24 in 2 weeks after PVE, with statistically significant differences (t=-6.019, -6.345, -3.933, P<0.05); the elevated percentages were respectively 80.1%, 19.9% and 23.8%. (3) Surgical and postoperative situations of hilar cholangiocarcinoma: of 11 patients, 10 received successful peri-hilar right hemihepatectomy, the right hepatic atrophy and an obvious demarcation line between left and right liver were found intraoperatively; 1 stopped operation due to detect intraoperatively peritoneal metastasis of tumor. The operation time, volume of intraoperative blood loss and time of postoperative abdominal drainage-tube removal were respectively (585±194)minutes, (472±274)mL and (8±5)days. Of 10 patients undergoing operations, 2 were complicated with massive peritoneal effusion at 2 days postoperatively, volume of peritoneal effusion remained more than 500 mL up to 7 days after drainage, and were improved by 1- month conservative treatment; other 8 patients were not complicated with hepatic dysfunction. Duration of hospital stay of 11 patients was (16±4)days. (4) Follow-up and survival situations: 10 patients were followed up for 4-72 months, with a median time of 39 months. During the follow-up, there was no evaluated TBil level and peritoneal effusion in 10 patients. The median survival time, 1-, 3- and 5-year overall survival rates were 88.8%, 74.6% and 36.8%, respectively. Conclusions The dynamic SPECT 99Tcm-GSA scintigraphy can effectively evaluate liver function changes of embolized and non-embolized lobes before and after PVE. The increased rate of FLV of non-embolized lobe is higher than that of MLV. Key words: Hilar cholangiocarcinoma; Radical resection; Portal vein embolization; Scintigraphy single-photon emission computed tomography; 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection; Regional liver function

Noninvasive quantitation of rat cerebral blood flow using 99mTc-HMPAO\u2014assessment of input function with dynamic chest planar imaging

BackgroundCerebral blood flow (CBF) quantitation using technetium-99m hexamethylpropyleneamine oxime (99mTc-HMPAO) generally requires assessment of input function by arterial blood sampling, which would be invasive for small animals. We therefore performed chest dynamic planar imaging, instead of arterial blood sampling, to estimate the input function and establish noninvasive quantitation method of rat CBF using the image-derived input function.ResultsIntegrated radioactivity concentration in the heart-blood pool on planar images (AUCBlood-planar) was identical to that in arterial blood samples (AUCBlood-sampling). Radioactivity concentration in the brain determined by SPECT imaging (CBrain-SPECT) was identical to that using brain sampling (CBrain-sampling). Noninvasively calculated CBF obtained by dividing CBrain-SPECT by AUCBlood-planar was well correlated with conventionally estimated CBF obtained by dividing CBrain-sampling by AUCBlood-sampling.ConclusionRat CBF could be noninvasively quantitated using 99mTc-HMPAO chest dynamic planar imaging and head SPECT imaging without arterial blood sampling.

First validation of myocardial flow reserve assessed by dynamic 99mTc-sestamibi CZT-SPECT camera: head to head comparison with 15O-water PET and fractional flow reserve in patients with suspected coronary artery disease. The WATERDAY study

PurposeWe assessed the feasibility of myocardial blood flow (MBF) and flow reserve (MFR) estimation using dynamic SPECT with a novel CZT camera in patients with stable CAD, in comparison with 15O–water PET and fractional flow reserve (FFR).MethodsThirty patients were prospectively included and underwent FFR measurements in the main coronary arteries (LAD, LCx, RCA). A stenosis ≥50% was considered obstructive and a FFR abnormal if ≤0.8. All patients underwent a dynamic rest/stress 99mTc-sestamibi CZT-SPECT and 15O–water PET for MBF and MFR calculation. Net retention kinetic modeling was applied to SPECT data to estimate global uptake values, and MBF was derived using Leppo correction. Ischemia by PET and CZT-SPECT was considered present if MFR was lower than 2 and 2.1, respectively.ResultsCZT-SPECT yielded higher stress and rest MBF compared to PET for global and LAD and LCx territories, but not in RCA territory. MFR was similar in global and each vessel territory for both modalities. The sensitivity, specificity, accuracy, positive and negative predictive value of CZT-SPECT were, respectively, 83.3, 95.8, 93.3, 100 and 85.7% for the detection of ischemia and 58.3, 84.6, 81.1, 36.8 and 93% for the detection of hemodynamically significant stenosis (FFR ≤ 0.8).ConclusionsDynamic 99mTc-sestamibi CZT-SPECT was technically feasible and provided similar MFR compared to 15O–water PET and high diagnostic value for detecting impaired MFR and abnormal FFR in patients with stable CAD.

Simplified Quantification and Acquisition Protocol for 123I-MIBG Dynamic SPECT

Previous studies have demonstrated the feasibility of absolute quantification of dynamic 123I-metaiodobenzylguanidine (123I-MIBG) SPECT imaging in humans. This work reports a simplified quantification method for dynamic 123I-MIBG SPECT using practical protocols with shortened acquisition time and voxel-by-voxel parametric imaging. Methods: Twelve healthy human volunteers underwent five 15-min dynamic SPECT scans at 0, 15, 90, 120, and 180 min after 123I-MIBG injection. List-mode SPECT data were binned into 29 frames and reconstructed with corrections for attenuation, scatter, and decay. Population-based blood-to-plasma correction and metabolite correction were applied to the image-derived input function. Likelihood estimation in graphical analysis (LEGA) was used as a simplified model to obtain volume of distribution (V T) values, which were compared with those obtained with the reversible 2-tissue (2T) compartment model. Three simplified protocols were evaluated with 2T and LEGA using a 30-min scan started simultaneously with tracer injection plus a 15-min scan at 90, 120, or 180 min after injection. Voxel-by-voxel LEGA fitting was applied to the aligned dynamic images using both the full protocol (five 15-min scans) and the simplified protocols. Results: Correlation analysis (y = 0.955x + 0.547, R 2 = 0.997) and Bland-Altman plot (mean difference, -0.8 mL/cm3; 95% limits of agreement, [-2.5, 1.0] mL/cm3; normal V T range, 29.0 ± 12.4 mL/cm3) showed that LEGA can be used as a simplified model of 2T for 123I-MIBG. High-quality V T parametric images could be obtained with LEGA. Region-of-interest (ROI) modeling and parametric imaging results were in excellent agreement as determined by correlation analysis (y = 0.999x - 1.026, R 2 = 0.982) and Bland-Altman plot (mean difference, -1.0 mL/cm3; 95% limits of agreement, [-4.2, 2.1] mL/cm3). V T correlated reasonably well between all simplified protocols and the full protocol with LEGA but not with 2T. The V T results were more reliable when there was a longer interval between the 2 acquisitions in the simplified protocols. Conclusion: For ROI-based kinetic modeling and parametric imaging, reliable quantification of dynamic 123I-MIBG SPECT can be achieved with LEGA using a simplified protocol of a 30-min scan starting with tracer injection plus a 15-min scan no earlier than 180 min after injection.

Initial value selection of the model parameters in the curve fitting phase of the dynamic SPECT imaging

Abstract The dynamic SPECT (Single Photon Emission Computed Tomography) reconstruction algorithm developed in our prior work reconstructs the parameters of the time activity curve for each image voxel directly from the projection images. In each iterations of the SPECT reconstruction beyond the static 3D MLEM (Maximum Likelihood Expectation Maximization) step, the algorithm performs a fitting process for each voxel in order to estimate the parameters describing the function of the examined organ considering that the time frames are not independent from each other. In real cases the fitted curve is nonlinear function of these parameters, it is usually described as the sum of exponential functions. In order to estimate the parameters properly, an iterative root-finding method is applied. In the current study the Newton-Raphson method is used. The selection of a proper initial value for the root-finding method is critical in order to achieve convergence of the fitting process. If the initial guess is not appropriate, the root-finding algorithm can diverge or converge to an inappropriate parameter set that can result in unacceptable reconstructed parameters. This affects then the subsequent MLEM iterations, also neighboring voxels and breaks the reconstruction. In this work we investigated different methods to calculate the initial values of the fitting process and evaluated the reconstructed parameter set of the dynamic SPECT reconstruction algorithm. Three different methods are investigated, one that uses the fitted parameters of the previous MLEM iteration, one that is based on the sum of the geometrical series of the exponentials and one that calculates the best guess using both methods. The three methods were compared by benchmark reconstruction cases using a mathematical phantom. In each reconstruction different initial value selection method was applied then the time activity curves of the voxels belonging to the same tissue were statistically evaluated using the reconstructed parameters. In the study no significant differences were found in the mean value of the reconstructed parameters. The standard deviation of the parameters was similar between the two simple approaches, however, the combination of the methods resulted in better statistical performance.

A Hybrid Active Contour Segmentation Method for Myocardial D-SPECT Images

The ischaemic heart disease has become one of the leading causes of mortality worldwide. Dynamic single-photon emission computed tomography (D-SPECT) is an advanced routine diagnostic tool commonly used to validate the myocardial function in patients suffering from various heart diseases. Accurate automatic localization and segmentation of myocardial regions is helpful in creating a 3-D myocardial model and assisting clinicians to perform assessments of myocardial function. Thus, image segmentation is a key technology in preclinical cardiac studies. Intensity inhomogeneity is one of the common challenges in image segmentation and is caused by image artifacts and instrument inaccuracy. In this paper, a novel region-based active contour model that can segment the myocardial D-SPECT image accurately is presented. First, a local region-based fitting image is defined based on the information related to the intensity. Second, a likelihood fitting image energy function is built in a local region around each point in a given vector-valued image. Next, the level set method is used to present a global energy function with respect to the neighborhood center. The proposed approach guarantees precision and computational efficiency by combining the region-scalable fitting energy model and local image fitting energy model, and it can solve the issue of high sensitivity to initialization for myocardial D-SPECT segmentation.

Dynamic SPECT reconstruction with temporal edge correlation

In dynamic imaging, a key challenge is to reconstruct image sequences with high temporal resolution from strong undersampling projections due to a relatively slow data acquisition speed. In this paper, we propose a variational model using the infimal convolution of Bregman distance with respect to total variation to model edge dependence of sequential frames. The proposed model is solved via an alternating iterative scheme, for which each subproblem is convex and can be solved by existing algorithms. The proposed model is formulated under both Gaussian and Poisson noise assumption and the simulation on two sets of dynamic images shows the advantage of the proposed method compared to previous methods.

Comparison of coronary flow reserve estimated by dynamic radionuclide SPECT and multi-detector x-ray CT

BackgroundRecent technical advances in multi-detector computed tomography (MDCT) allow for assessment of coronary flow reserve (CFR). We compared regional CFR by dynamic SPECT and by dynamic MDCT in patients with suspected or known coronary artery disease (CAD). MethodsThirty-five patients, (29 males, mean age 69 years) with greater than average Framingham risk of CAD, underwent dipyridamole vasodilator stress imaging. CFR was estimated using dynamic SPECT and dynamic MDCT imaging in the same patients. Myocardial perfusion findings were correlated with obstructive CAD (≥50% luminal narrowing) on CT coronary angiography (CA). ResultsMean CFR estimated by SPECT and MDCT in 595 myocardial segments was not different (1.51 ± 0.46 vs. 1.50 ± 0.37, p = NS). Correlation of segmental CFR by SPECT and MDCT was fair (r2 = 0.39, p < 0.001). Bland-Altman analysis revealed that MDCT in comparison to SPECT systematically underestimated CFR in higher CFR ranges. By CTCA, 12 patients had normal CA, 11 had non-obstructive, and 12 had obstructive CAD. CFR by both techniques was significantly higher in territories of normal CA than in territories subtended by non-obstructive or obstructive CAD. SPECT CFR was also significantly different in territories subtended by non-obstructive and obstructive CAD, whereas MDCT CFR was not. ConclusionDespite relative underestimation of high CFR values, MDCT CFR shows promise for assessing the pathophysiological significance of anatomic CAD.

Noninvasive Nuclear SPECT Myocardial Blood Flow Quantitation to Guide Management for Coronary Artery Disease.

Recently, myocardial blood flow quantitation with dynamic SPECT has been validated to enhance the detection of multivessel coronary artery disease (CAD) and conclude equivocal SPECT myocardial perfusion study. This advance opened an important clinical application to utilize the tool in guiding CAD management for area where myocardial perfusion tracers for PET are unavailable or unaffordable. We present a clinical patient with ongoing recursive angina who underwent multiple nuclear stress tests for a sequence of CAD evaluation in 26 months and demonstrated that SPECT myocardial blood flow quantitation properly guided CAD management to warrant patient outcome.

Quantification of myocardial perfusion reserve using dynamic SPECT images of patients with chronic kidney disease

BackgroundChronic kidney disease (CKD) is an independent risk factor for cardiovascular disorders. The aim of this study was to examine whether the quantitatively measured myocardial blood flow (MBF) or myocardial perfusion reserve (MPR), calculated by dynamic single photon emission computed tomography (SPECT) analysis using a cardiac cadmium zinc telluride (CZT) gamma camera, was related to renal dysfunction in patients with normal myocardial perfusion imaging (MPI) findings. MethodsThe study population consisted of 46 patients with CKD and 46 individuals without CKD (controls). Their MPR index was quantitatively measured using adenosine MPI with a cardiac CZT gamma camera. All assessments were with a single tissue compartment kinetic model. The K1 value was calculated on stress and at-rest images. To obtain the MPR index we divided K1 stress-by K1 at-rest values. ResultsThe at-rest K1 value was significantly higher and the MPR index was significantly lower in patients with CKD than those without CKD [CKD vs. controls: at-rest K1 value, 0.21 (0.17–0.25) vs. 0.19 (0.16–0.22), p=0.040; MPR index, 1.86 (1.69–2.22) vs. 2.19 (1.93–2.41), p<0.001]. The stress K1 values were not significantly different. ConclusionThe MPR index is significantly lower in CKD patients; this is considered as being mainly due to an increase in the at-rest K1 value.

Coronary Flow Reserve Assessment in Patients with Cad by Dynamic Single-Photon Emission Computed Tomography

Purpose: to assess the coronary flow reserve in patients with one, two and multi-vessel coronary artery diseases by dynamic SPECT using semiconductor (cadmium-zinctelluride)- based gamma camera.Material and methods.This work included 42 patients with stable coronary artery diseases. The first group consisted of 12 (28.6%) patients with single and two-vessel coronary artery disease (STCAD) (8 males and 4 females; mean age 61.5 ± 3.8 years) with intermediate (50–70%) and significant (&gt;70%) coronary artery stenosis. Second group included 30 (71.4%) patients with multi- vessel coronary artery diseases (MVCAD) (22 males and 8 females; mean age 60.1 ± 4.3 years) with a lesion &gt;70% in at least 2 major epicardial vessels according to invasive coronary angiography. All patients underwent rest-stress dynamic SPECT as well as conventional myocardial perfusion imaging with 99mTc-MIBI as a radiopharmaceutical. All scintigraphic images were acquired on the hybrid SPECT/CT unit (GE Discovery NM/CT 570C). Patient with STCAD underwent invasive FFR detection.Results.When comparing the results of MPI between the study groups, there were no significant differences. ROC analysis showed that the global MFR ≤ 1,42 allows to identify MVCAD with a sensitivity and specificity 68% and 86,4%, for PSM, these values are: 39.1% and 86.4% (AUC = 0.655, p &lt; 0.05), respectively (“gold” standard CAG). The sensitivity and specificity of the regional MFR to identify the hemodynamic significance of coronary artery stenoses at a value of &lt;1.33 was 100% (the “gold” standard of FFR). Most likely, high sensitivity and specificity in this case are associated with a small number of patients with true stenoses of FFR.Conclusion.The performance of standard MPI in combination with dynamic single-photon emission computed tomography allows to increase the diagnostic significance of the scintigraphic approach in the evaluation of myocardial microcirculation disorders in multivessel coronary artery disease. Dynamic SPECT is a promising method of noninvasive assessment of hemodynamic significance of coronary artery stenoses.

Single-scan rest/stress imaging with 99mTc-Sestamibi and cadmium zinc telluride-based SPECT for hyperemic flow quantification: A feasibility study evaluated with cardiac magnetic resonance imaging.

IntroductionWe aimed to evaluate whether the hyperemic myocardial blood flow (MBF) can be estimated using cadmium zinc telluride (CZT)-based single-photon emission computed tomography (SPECT) cameras with a single, rapid rest/stress dynamic scan. Dynamic contrast-enhanced (DCE) cardiac magnetic resonance imaging (MRI) was used as a reference modality for flow measurement.Materials and methodsThe proposed protocol included both the rest and stress acquisitions within a 24-min scan. Patients were first injected with 99mTc-Sestamibi at the resting state. Sixty minutes after the first injection, the subject was positioned via scintigraphy, after which the list-mode data acquisition was initiated and continued for 24 minutes. Five minutes after data acquisition was initiated, a stressed state was induced via dipyridamole infusion, after which a second dose of 99mTc-Sestamibi was injected. Dynamic SPECT images were reconstructed for all subjects, who also underwent T1-weighted cardiac DCE-MRI performed on days other than those of the SPECT studies. MBF values were estimated for the rest and stress MRI studies, and for the stress portion of the SPECT study. The SPECT-measured hyperemic MBF was compared with the MR-measured hyperemic MBF and coronary flow reserve (CFR), based on the regions of interest.ResultsA total of 30 subjects were included in this study. The hyperemic MBF estimated from SPECT showed a strong correlation with the MR-measured hyperemic MBF (r2 = 0.76) and a modest correlation with the MR-measured CFR (r2 = 0.56). Using MR-measured CFR <1.3 as a cutoff for coronary stenosis, we found that the SPECT-measured hyperemic MBF served as a useful clinical index with 94% sensitivity, 90% specificity, and 93% accuracy.ConclusionsHyperemic MBF can be measured with a rapid, single-scan rest/stress study with CZT-based SPECT cameras.

Avoiding full corrections in dynamic SPECT images impacts the performance of SPECT myocardial blood flow quantitation

IntroductionThis study investigated the performance of SPECT myocardial blood flow (MBF) quantitation lacking full physical corrections (All Corr) in dynamic SPECT (DySPECT) images. MethodsEleven healthy normal volunteers (HVT) and twenty-four patients with angiography-documented CAD were assessed. All Corr in 99mTc-sestamibi DySPECT encompassed noise reduction (NR), resolution recovery (RR), and corrections for scatter (SC) and attenuation (AC), otherwise no correction (NC) or only partial corrections. The performance was evaluated by quality index (R2) and blood-pool spillover index (FBV) in kinetic modeling, and by rest flow (RMBF) and stress flow (SMBF) compared with those of All Corr. ResultsIn HVT group, NC diminished 2-fold flow uniformity with the most degraded quality (15%-18% reduced R2) and elevated spillover effect (45%-50% increased FBV). Consistently higher RMBF and SMBF were discovered in both groups (HVT 1.54/2.31 higher; CAD 1.60/1.72; all P < .0001). Bland-Altman analysis revealed positive flow bias (HVT 0.9-2.6 mL/min/g; CAD 0.7-1.3) with wide ranges of 95% CI of agreement (HVT NC −1.9-7.1; NR −0.4-4.4; NR + SC −1.1-4.3; NR + SC + RR −0.7-2.5) (CAD NC −1.2-3.8; NR −1.0-2.8; NR + SC −1.0-2.5; NR + SC + RR −1.1-2.6). ConclusionsUncorrected physical interference in DySPECT images can extensively impact the performance of MBF quantitation. Full physical corrections should be considered to warrant this tool for clinical utilization.

A Direct Method for Reconstructing Dynamic SPECT Images

The goal in dynamic SPECT studies is to estimate the time-activity functions describing the tracer activity changes in the observed tissue. Dynamic studies can be created as a series of static projection images recorded in several subsequent time frames. By applying a static reconstruction algorithm for each images independently and fitting the parameters of a kinetic model to the activity on the reconstructed images we can estimate the function of the tracer activity changes. However, due to the limited data collection time images in dynamic studies often suffer from poor statistics influencing the accuracy of the kinetic function estimation. According to previous studies improved function reconstruction can be achieved by applying reconstruction algorithms that estimate kinetic parameters directly from the measured projection data. In this study our previously developed Monte Carlo based maximum likelihood expectation maximization (ML-EM) SPECT reconstruction method - originally verified for static SPECT studies - is extended for dynamic studies. An iterative dynamic reconstruction algorithm is developed that estimates directly the temporal function of the tracer activity in the image voxels in each iterations and uses the static ML-EM iteration afterwards. The method of sieves has been applied for regularization of the estimated kinetic parameters. The estimation accuracy of the suggested dynamic reconstruction algorithm was evaluated in a mathematical phantom study with different time functions.

Estimation of myocardial flow reserve utilizing an ultrafast cardiac SPECT: Comparison with coronary angiography, fractional flow reserve, and the SYNTAX score

BackgroundQuantitative assessment of myocardial flow reserve (MFR) by single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is challenging but may facilitate evaluation of multi-vessel coronary artery disease (CAD). MethodsWe enrolled 153 patients with suspected or known CAD, referred for pharmacological stress MPI. They underwent a 99mTc-perfusion stress/rest SPECT with an ultrafast cadmium-zinc-telluride (CZT) camera. Dynamic data were acquired and time-activity curves fitted to a 1-tissue compartment analysis with input function. K1 was assigned for stress and rest data. The MFR index (MFRi) was calculated as K1 stress/K1 at-rest. The findings were validated by invasive coronary angiography in 69 consecutive patients. ResultsThe global MFRi was 1.46 (1.16–1.76), 1.33 (1.12–1.54), and 1.18 (1.01–1.35), for 1-vessel disease (VD), 2-VD, and 3-VD, respectively. In the 3-VD, global MFRi was lower than that in 0-VD (1.63 [1.22–2.04], P<0.0001) and 1-VD (P=0.003). Multivariate logistic regression analysis for 3-VD showed significant associations with smoking history (odds ratio [OR]: 4.4 [0.4–8.4]), left ventricular ejection fraction (OR: 61.6 [57.5–66.0]), and global MFRi (OR: 119.6 [111.5–127.7], P=0.002). A cut-off value of 1.3 yielded 93.3% sensitivity and 75.9% specificity for diagnosing 3-VD. Fractional flow reserve positively correlated with regional MFRi (r=0.62, P=0.008), and the SYNTAX score correlated negatively with global MFRi (r=0.567, P=0.0003). ConclusionWe developed and validated a clinically available method for MFR quantification by dynamic 99mTc-perfusion SPECT utilizing a CZT camera, which improves the detectability of multi-vessel CAD.

Design of a short nonuniform acquisition protocol for quantitative analysis in dynamic cardiac SPECT imaging - a retrospective 123 I-MIBG animal study.

Our previous works have found that quantitative analysis of 123 I-MIBG kinetics in the rat heart with dynamic single-photon emission computed tomography (SPECT) offers the potential to quantify the innervation integrity at an early stage of left ventricular hypertrophy. However, conventional protocols involving a long acquisition time for dynamic imaging reduce the animal survival rate and thus make longitudinal analysis difficult. The goal of this work was to develop a procedure to reduce the total acquisition time by selecting nonuniform acquisition times for projection views while maintaining the accuracy and precision of estimated physiologic parameters. Taking dynamic cardiac imaging with 123 I-MIBG in rats as an example, we generated time activity curves (TACs) of regions of interest (ROIs) as ground truths based on a direct four-dimensional reconstruction of experimental data acquired from a rotating SPECT camera, where TACs represented as the coefficients of B-spline basis functions were used to estimate compartmental model parameters. By iteratively adjusting the knots (i.e., control points) of B-spline basis functions, new TACs were created according to two rules: accuracy and precision. The accuracy criterion allocates the knots to achieve low relative entropy between the estimated left ventricular blood pool TAC and its ground truth so that the estimated input function approximates its real value and thus the procedure yields an accurate estimate of model parameters. The precision criterion, via the D-optimal method, forces the estimated parameters to be as precise as possible, with minimum variances. Based on the final knots obtained, a new protocol of 30 min was built with a shorter acquisition time that maintained a 5% error in estimating rate constants of the compartment model. This was evaluated through digital simulations. The simulation results showed that our method was able to reduce the acquisition time from 100 to 30 min for the cardiac study of rats with 123 I-MIBG. Compared to a uniform interval dynamic SPECT protocol (1 s acquisition interval, 30 min acquisition time), the newly proposed protocol with nonuniform interval achieved comparable (K1 and k2, P = 0.5745 for K1 and P = 0.0604 for k2) or better (Distribution Volume, DV, P = 0.0004) performance for parameter estimates with less storage and shorter computational time. In this study, a procedure was devised to shorten the acquisition time while maintaining the accuracy and precision of estimated physiologic parameters in dynamic SPECT imaging. The procedure was designed for 123 I-MIBG cardiac imaging in rat studies; however, it has the potential to be extended to other applications, including patient studies involving the acquisition of dynamic SPECT data.

High-throughput high-volume nuclear imaging for preclinical in vivo compound screening\xa7

BackgroundPreclinical single-photon emission computed tomography (SPECT)/CT imaging studies are hampered by low throughput, hence are found typically within small volume feasibility studies. Here, imaging and image analysis procedures are presented that allow profiling of a large volume of radiolabelled compounds within a reasonably short total study time. Particular emphasis was put on quality control (QC) and on fast and unbiased image analysis.Methods2–3 His-tagged proteins were simultaneously radiolabelled by 99mTc-tricarbonyl methodology and injected intravenously (20 nmol/kg; 100 MBq; n = 3) into patient-derived xenograft (PDX) mouse models. Whole-body SPECT/CT images of 3 mice simultaneously were acquired 1, 4, and 24 h post-injection, extended to 48 h and/or by 0–2 h dynamic SPECT for pre-selected compounds. Organ uptake was quantified by automated multi-atlas and manual segmentations. Data were plotted automatically, quality controlled and stored on a collaborative image management platform. Ex vivo uptake data were collected semi-automatically and analysis performed as for imaging data.Results>500 single animal SPECT images were acquired for 25 proteins over 5 weeks, eventually generating >3500 ROI and >1000 items of tissue data. SPECT/CT images clearly visualized uptake in tumour and other tissues even at 48 h post-injection. Intersubject uptake variability was typically 13% (coefficient of variation, COV). Imaging results correlated well with ex vivo data.ConclusionsThe large data set of tumour, background and systemic uptake/clearance data from 75 mice for 25 compounds allows identification of compounds of interest. The number of animals required was reduced considerably by longitudinal imaging compared to dissection experiments. All experimental work and analyses were accomplished within 3 months expected to be compatible with drug development programmes. QC along all workflow steps, blinding of the imaging contract research organization to compound properties and automation provide confidence in the data set. Additional ex vivo data were useful as a control but could be omitted from future studies in the same centre. For even larger compound libraries, radiolabelling could be expedited and the number of imaging time points adapted to increase weekly throughput. Multi-atlas segmentation could be expanded via SPECT/MRI; however, this would require an MRI-compatible mouse hotel. Finally, analysis of nuclear images of radiopharmaceuticals in clinical trials may benefit from the automated analysis procedures developed.

Ядерная медицина в диагностике ангиопатий у пациентов с сахарным диабетом второго типа

Purpose: To determine the role of nuclear medicine techniques in the early detection of angiopathy in patients with diabetes and to estimate their accuracy in comparison with routine diagnostic methods for evaluation of target organ damage.&#x0D; Material and methods: A literature review, selected from the Russian and international bibliographic databases (RSCI, Medline, Google Scholar), dedicated to diagnostic technologies for identification of angiopathy in patients with diabetes mellitus.&#x0D; Results: 193 sources dedicated to the diagnosis of micro- and macrovascular damage were analyzed, 66 of which were included in this study, 54 of them international and 12 domestic ones responding to the purpose of the study. The analysis revealed that the radionuclide methods of investigation reflecting the functional state of the tissues were evaluated in a small number of publications on early diagnosis angiopathy caused by diabetes mellitus type 2. Most often, high blood glucose concentration damages kidney tissue and myocardium. It is shown that the methods of dynamic nephroscintigraphy and ECG-&#x0D; gated myocardial perfusion SPECT allow to evaluate the progression of micro- and macrovascular disease before the manifestation of paraclinical signs according to other diagnostic methods. Key determined parameter in dynamic nephroscintigraphy is glomerular filtration rate, which declines on the early stages of the disease. Myocardial perfusion SPECT imaging provides a possibility to assess frequency and severity of ischemic myocardial injury.&#x0D; Conclusions: The use of nuclear medicine techniques in the diagnosis of angiopathy in diabetes allows verification of early damage to target organs. The most effective diagnostic methods for this purpose are dynamic nephroscintigraphy and myocardial perfusion SPECT which sensitivity is substantially higher than conventional diagnostic methods.

Validation of a Multimodality Flow Phantom and Its Application for Assessment of Dynamic SPECT and PET Technologies.

Simple and robust techniques are lacking to assess performance of flow quantification using dynamic imaging. We therefore developed a method to qualify flow quantification technologies using a physical compartment exchange phantom and image analysis tool. We validate and demonstrate utility of this method using dynamic PET and SPECT. Dynamic image sequences were acquired on two PET/CT and a cardiac dedicated SPECT (with and without attenuation and scatter corrections) systems. A two-compartment exchange model was fit to image derived time-activity curves to quantify flow rates. Flowmeter measured flow rates (20-300 mL/min) were set prior to imaging and were used as reference truth to which image derived flow rates were compared. Both PET cameras had excellent agreement with truth ( [Formula: see text]). High-end PET had no significant bias (p > 0.05) while lower-end PET had minimal slope bias (wash-in and wash-out slopes were 1.02 and 1.01) but no significant reduction in precision relative to high-end PET (<15% vs. <14% limits of agreement, p > 0.3). SPECT (without scatter and attenuation corrections) slope biases were noted (0.85 and 1.32) and attributed to camera saturation in early time frames. Analysis of wash-out rates from non-saturated, late time frames resulted in excellent agreement with truth ( [Formula: see text], slope = 0.97). Attenuation and scatter corrections did not significantly impact SPECT performance. The proposed phantom, software and quality assurance paradigm can be used to qualify imaging instrumentation and protocols for quantification of kinetic rate parameters using dynamic imaging.

A single-scan protocol for absolute D2/3 receptor quantification with [123I]IBZM SPECT

PurposeMolecular imaging of the D2/3 receptor is widely used in neuropsychiatric research. Non-displaceable binding potential (BPND) is a very popular quantitative index, defined as the product of the receptor concentration (Bavail) and the radiotracer affinity for the receptor (1/appKd). As the appKd is influenced by parameters such as the endogenous neurotransmitter dynamics, it often constitutes a confounding factor in research studies. A simplified method for absolute quantification of both these parameters would be of great interest in this context. Here, we describe the use of a partial saturation protocol that permits to produce an in vivo Scatchard plot and thus estimate Bavail and appKd separately, through a single dynamic SPECT session. To validate this approach, a multi-injection protocol is used for the full kinetic modeling of [123I]IBZM using a 3-tissue compartment, 7-parameter model (3T-7k). Finally, more “classic” BPND estimation methods are also validated against the results of the 3T-7k. MethodsTwenty-nine male rats were used. Binding parameters were estimated using the 3T-7k in a multi-injection protocol. A partial saturation protocol was applied at the region- and voxel-level and results were compared to those obtained with the 3T-7k model. The partial saturation protocol was applied after an adenovirus-mediated D2 receptor striatal overexpression and in an amphetamine-induced dopamine release paradigm. The Simplified Reference Tissue Model (SRTM), the Logan's non-invasive graphical analysis (LNIGA) and a simple standardized uptake ratio (SUR) method were equally applied. ResultsThe partial saturation experiments gave similar values as the 3T-7k both at the regional and voxel-level. After adenoviral-mediated D2-receptor overexpression, an increase in Bavail by approximately 18% was observed in the striatum. After amphetamine administration, a 16.93% decrease in Bavail (p<0.05) and a 39.12% increase (p<0.01) in appKd was observed. BPND derived from SRTM, LNIGA and SUR correlated well with the Bavail values from the 3T-7k (r=0.84, r=0.84 and r=0.83, respectively, p<0.0001 for all correlations). ConclusionA partial saturation protocol permits the non-invasive and time-efficient estimation of Bavail and appKd separately. Given the different biological phenomena that underlie these parameters, this method may be applied for the in-depth study of the dopaminergic system in translational molecular imaging studies. It can detect the biological variations in these parameters, dissociating the variations in receptor density (Bavail) from affinity (1/appKd), which reflects the interactions of the receptor with its endogenous ligand.