Diagnostic approach with Z-score mapping to reduce artifacts caused by cerebral atrophy in regional CBF assessment of mild cognitive impairment (MCI) and Alzheimer's disease by [99mTc]-ECD and SPECT.

PURPOSE: The aim of this study was to develop a novel approach that enhanced diagnostic accuracy in the diagnosis of mild cognitive impairment (MCI) and early Alzheimer's disease (AD) using cerebral perfusion SPECT by minimizing artifacts caused by cerebral atrophy. MATERIALS AND METHODS: [99mTc]-ECD and SPECT studies were performed on 15 cognitively normal patients, 40 patients with MCI, and 16 patients with AD. SPECT images were compared using SPM. The atrophy correction method was incorporated to reduce artifacts through the MRI masking procedure. Regional Z-score, percent extent, and atrophy correction rate were obtained and compared. The Z-score mapping program was structured as a single package that ran semi-automatically. RESULTS: The method significantly reduced regional Z-score in most regions, leading to improved estimates. The mean atrophy correction rate ranged from 10.4 to 12.0%. In MCI and AD, the convexities of the frontal and parietal lobes and the posterior medial cerebrum were particularly sensitive to cerebral atrophy, and the Z-scores were overestimated, whereas the posterior cingulate cortex and the cerebellum were less sensitive. The diagnostic accuracy for MCI increased from 67 to 69% and for AD from 78 to 82%. CONCLUSION: The proposed approach provided more precise Z-scores with less over- or underestimation, artifacts, and improved diagnostic accuracy, being recommended for clinical studies.

Machine learning-based prediction of conversion coefficients for I-123 metaiodobenzylguanidine heart-to-mediastinum ratio.

PURPOSE: We developed a method of standardizing the heart-to-mediastinal ratio in 123I-labeled meta-iodobenzylguanidine (MIBG) images using a conversion coefficient derived from a dedicated phantom. This study aimed to create a machine-learning (ML) model to estimate conversion coefficients without using a phantom. METHODS: 210 Monte Carlo (MC) simulations of 123I-MIBG images to obtain conversion coefficients using collimators that differed in terms of hole diameter, septal thickness, and length. Simulated conversion coefficients and collimator parameters were prepared as training datasets, then a gradient-boosting ML was trained to estimate conversion coefficients from collimator parameters. Conversion coefficients derived by ML were compared with those that were MC simulated and experimentally derived from 613 phantom images. RESULTS: Conversion coefficients were superior when estimated by ML compared with the classical multiple linear regression model (root mean square deviations: 0.021 and 0.059, respectively). The experimental, MC simulated, and ML-estimated conversion coefficients agreed, being, respectively, 0.54, 0.55, and 0.55 for the low-; 0.74, 0.70, and 0.72 for the low-middle; and 0.88, 0.88, and 0.88 for the medium-energy collimators. CONCLUSIONS: The ML model estimated conversion coefficients without the need for phantom experiments. This means that conversion coefficients were comparable when estimated based on collimator parameters and on experiments.

Automatic quantification package (Hone Graph) for phantom-based image quality assessment in bone SPECT: computerized automatic classification of detectability.

OBJECTIVE: We previously developed a custom-design thoracic bone scintigraphy-specific phantom ("SIM2 bone phantom") to assess image quality in bone single-photon emission computed tomography (SPECT). We aimed to develop an automatic assessment system for imaging technology in bone SPECT and demonstrate the validity of this system. METHODS: Four spherical lesions of 13-, 17-, 22-, and 28-mm diameters in the vertebrae of SIM2 bone phantom simulating the thorax were filled with radioactivity (target-to-background ratio: 4). Dynamic SPECT acquisitions were performed for 15 min; reconstructions were performed using ordered subset expectation maximization at 3-15-min timepoints. Consequently, 216 lesions (54 SPECT images) were obtained: 120 and 96 lesions were used for software development and validation, respectively. The developed software used statistical parametric mapping to rigidly register and automatically calculate quantitative indexes (contrast-to-noise ratio, % coefficient of variance, % detectability equivalence volume, recovery coefficient, target-to-normal bone ratio, and full width at half maximum). A detectability score (DS) was used to define the four observation types (4, excellent; 3, adequate; 2, average; 1, poor) to score hot spherical lesions. The gold standard for DSs was independently classified by three experienced board-certified nuclear medicine technologists using the four observation types; thereafter, a consensus regarding the gold standard for DSs was reached. Using 120 lesions for development, decision tree analysis was performed to determine DS based on the quantitative indexes. We verified the validation of the quantitative indexes and their threshold values for automatic classification using 96 lesions for validation. RESULTS: The trends in the automatically calculated quantitative indices were consistent. Decision tree analysis produced four terminal groups; two quantitative indexes (% detectability equivalence volume and contrast-to-noise ratio) were used to classify DS. The automatically classified DSs exhibited an almost perfect agreement with the gold standard. The percentage agreement and kappa coefficient were 91.7% and 0.93, respectively, in 96 lesions for validation. CONCLUSIONS: The developed software automatically classified the detectability of hot lesions in the SIM2 bone phantom using the automatically calculated quantitative indexes, suggesting that this software could provide a means to automatically perform detectability analysis after data input that is excellent in reproducibility and accuracy.

Prediction of Cognitive Decline from White Matter Hyperintensity and Single-Photon Emission Computed Tomography in Alzheimer's Disease.

BACKGROUND: While several studies support an association of white matter hyperintensity (WMH) volume and regional cerebral blood flow (rCBF) with cognitive decline in Alzheimer's disease (AD), no reports have simultaneously considered the effects of both factors on cognitive decline. OBJECTIVE: The purpose of the present study was to compare WMH volume and rCBF in relation to cognitive function by developing a new software program to fuse magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) data. METHOD: We used MRI, SPECT, and neuropsychological data from 182 serial outpatients treated at the memory clinic of our hospital. RESULTS: Twenty-nine AD patients fulfilled the inclusion criteria (18 females, mean age: 73.1 ± 7.9 years, mean Mini-Mental State Examination: 23.1 ± 3.0). Analysis of variance revealed that posterior deep WMH (DWMH) volume was significantly larger than both anterior periventricular hyperintensity (PVH) and DWMH, and posterior PVH volumes. Multivariate regression analysis showed that increased volumes of the anterior PVH and the posterior DWMH and decreased rCBF of the parietal cortex negatively affected cognitive function. The other areas had no significant negative effects on cognitive function. CONCLUSION: Our findings show that the volume of the posterior WMH was significantly larger than that of other areas, and the increased posterior WMH volume and decreased rCBF of the parietal cortex negatively affected cognitive function. Therefore, the posterior WMH volume and the parietal rCBF are key parameters of cognitive decline in AD patients.

Simplified estimation of binding parameters based on image-derived reference tissue models for dopamine transporter bindings in non-human primates using [18F]FE-PE2I and PET.

The aim of this study on dopamine transporter binding by [18F]FE-PE2I and PET was to describe an image-derived approach using reference tissue models: the Logan DVR approach and simplified reference tissue model (SRTM), the features of which were simple to operate and precise in the measurements. Using the approach, the authors sought to obtain binding images and parameters. [18F]FE-PE2I and dynamic PET as well as an MRI was performed on three rhesus monkeys, and metabolite corrected arterial plasma inputs were obtained. After co-registering of PET to MR images, both image sets were resliced. The time-activity curve of the cerebellum was used as indirect input, and binding parametric images were computed voxel-by-voxel. Voxel-wise linear calculations were used for the Logan DVR approach, and nonlinear least squares fittings for the SRTM. To determine the best linear regression in the Logan DVR approach, the distribution volume ratio was obtained using the optimal starting frame analysis. The obtained binding parameters were compared with those obtained by the other independent ROI-based numerical approaches: two-tissue compartment model (2TCM), Logan DVR approach and SRTM using PMOD software. Binding potentials (BP) obtained by the present approach agreed well with those obtained by ROI-based numerical approaches, although reference tissue models tended to underestimate the BP value than 2TCM. Image-derived Logan approach provided a low-noise image, the computation time was short, and the error in the optimal starting frame analysis was small. The present approach provides a high-quality binding parametric image and reliable parameter value easily.

[Determination of the optimal ROI setting position of the input function for the 99mTc-ethyl cysteinate dimmer brain uptake ratio method].

Determination of the input function for the (99m)Tc-ethyl cysteinate dimmer brain uptake ratio ((99m)Tc-ECD BUR) method as a non-invasive quantitative measurement of cerebral blood flow measurement is of critical importance in order to improve the accuracy of this method. The input functions were experimentally obtained by setting the regions of interest (ROIs) in the ascending aorta, aortic arch, and descending aorta on the 49 chest RI-angio images. rCBFs by the BUR method with 3 input functions of the 6 cases were compared with those by the (123)I-iodoamphetamine (IMP) continuous arterial blood sampling method in order to determine the best location for the ROI of the input function. The input function of the ascending aorta was higher than those of the aortic arch and the descending aorta. The input functions of the aortic arch and the descending aorta decreased due to the origin of the three branches of the right brachiocephalic artery, left subclavian artery, and left common carotid artery. A good correlation was found in the regional cerebral blood flow (rCBF) values between the (123)I-IMP continuous arterial blood sampling method and the (99m)Tc-ECD BUR method with the input function of the ascending aorta. Therefore, the ascending aorta is the best location for the ROI of the input function for the (99m)Tc-ECD BUR method.

Improvement of the (99m)Tc-ECD brain uptake ratio (BUR) method for measurement of cerebral blood flow.

OBJECTIVE: The brain uptake ratio (BUR) method for the (99m)Tc-ECD SPECT, a non-invasive measurement method of rCBF, has been used in clinical practice in Japan, because it is simple to use. However, the accuracy of this method is limited, as it has problems in the determination of input function and the regression equation. The purpose of this study is to improve the BUR method by reconstructing the determination process of the input function and regression equation based on measurement of the rCBF by H (2) (15) O PET. METHOD: The input function was obtained by setting the region of interest on the ascending aorta instead of the aortic arch. The 3DSRT algorithm was used to obtain the anatomically standardized rCBF, and developed a semi-automatic analyzing software using C++ in order to stabilize the repeatability of the improved BUR (IBUR) method. The regression equation for the IBUR method was obtained by the H (2) (15) O PET rCBFs in 15 patients with the arterial blood sampling method. All the measurements in this study were performed with the patient in the resting state. RESULT: A good correlation was observed between the rCBF values measured by H (2) (15) O PET and the regional BURs measured by the IBUR method (r = 0.86, p < 0.0001). The rCBF values were calculated for only 5 min using a semi-automatic analyzing software. CONCLUSION: The BUR method was improved by changing the location of the input function from the aortic arch to the ascending aorta based on arterial blood flow dynamics, and reconstructing regression equation based on the rCBF values obtained using H (2) (15) O PET. This finding indicates the potential clinical usefulness of this method.

Quantification of myocardial perfusion SPECT using freeware package (cardioBull).

OBJECTIVE: We have developed freeware package for automatically quantifying myocardial perfusion and (123)I-labeled radiopharmaceutical single-photon emission computed tomography (SPECT), which is called "cardioBull". We aim to evaluate diagnostic performance of the detection of coronary artery disease (CAD) on the developed software in comparison with commercially available software package [Quantitative Perfusion SPECT (QPS)]. METHODS: Stress-rest (99m)Tc-sestamibi myocardial perfusion SPECT was performed in 36 patients with CAD and 35 control patients. A ≥ 75% stenosis in the coronary artery was identified by coronary angiography in the CAD group. Segmental perfusion defect score was automatically calculated by both cardioBull and QPS software. Summed stress score (SSS) was obtained to detect CAD by the receiver operator characteristic (ROC) analysis. Areas under the ROC curves (AUC) were calculated in patient-based and coronary-based analyses. RESULTS: Mean SSSs showed no significant difference between cardioBull and QPS (6.0 ± 7.1 vs. 5.6 ± 7.0). The AUC for cardioBull was equivalent to that for QPS (0.91 ± 0.04 vs. 0.87 ± 0.04, p = n.s.). Sensitivity, specificity, and accuracy for cardioBull were 89, 74, and 82%, respectively. For the regional detection of CAD, the AUC showed largest value in left anterior descending coronary artery (LAD) territory (0.86 ± 0.06 for cardioBull, 0.87 ± 0.06 for QPS, p = n.s.). Sensitivity, specificity and accuracy of cardioBull were 70, 88, and 83% for the LAD; 91, 62, and 66% for the left circumflex coronary artery (LCx); and 78, 69, and 70% for the right coronary artery (RCA), respectively. CONCLUSIONS: The AUC, sensitivity, specificity and accuracy for the detection of CAD showed high diagnostic performance on the developed software. In addition, the developed software provided comparable diagnostic performance to the commercially available software package.

Esophageal transit study using a sliding sum image: application to patients with probable and definite systemic sclerosis.

PURPOSE: Esophageal complication is common in systemic sclerosis (SSc), but scintigraphic transit patterns based on each subtype have not been understood well. The aim of this study was to develop a new algorithm for integrating a dynamic esophageal transit study and to apply the method to patients with SSc. METHODS: A total of 40 patients suspected of having SSc were examined by a dynamic esophageal transit study. The subtypes included 32 with definite SSc (15 limited cutaneous type and 17 diffuse cutaneous type) and 8 with probable SSc. The serial esophageal images were shifted and summed to a functional image (sliding sum image) and compared to a conventional condensed image analysis. Esophageal retention fraction at 90 s (R (90)) and half-time (T (1/2)) of transit were also measured. RESULTS: The four patterns of the sliding sum image and condensed image agreed in all patients. Abnormal retention patterns were observed in none of the 8 (0%) patients with the probable SSc and in 15 of 32 (47%) patients with definite SSc (p = 0.014). The severity of scleroderma assessed by modified Rodnan skin thickness score correlated with that of esophageal retention R (90) (p = 0.04). CONCLUSION: The sliding sum image is a simple and effective method for integrating esophageal transit. Patients with definite SSc and severe scleroderma had significantly higher retention patterns, while probable SSc patients showed no esophageal dysmotility.

Semi-automated algorithm for calculating heart-to-mediastinum ratio in cardiac Iodine-123 MIBG imaging.

BACKGROUND: We have developed novel software for semi-automatically measuring heart-to-mediastinum (H/M) ratio in cardiac Iodine-123 (¹²³I)-labeled meta-iodobenzylguanidine (MIBG) imaging. Our aim is to improve the reproducibility of the H/M ratio using the semi-automated method as opposed to the manual method. METHODS AND RESULTS: The software algorithm automatically determined the mediastinal region of interest (ROI) using information from ¹²³I-MIBG uptake of the heart, lung, liver, and thyroid after a cardiac circular ROI was manually set. A total of 37 patients who underwent both early and delayed ¹²³I-MIBG imaging was retrospectively selected. The heart-to-mediastinum (H/M) ratios were calculated by both semi-automated and manual methods and assessed for the intra- and inter-observer variability. All H/M ratios were classified into three groups: normal, slight abnormality, and severe abnormality. The H/M ratios with the new method were higher than those obtained manually (P < .001). In the test-retest reliability, the intra-class correlation coefficient from the semi-automated method showed excellent reproducibility for early (0.99) and delayed (0.99) imaging. The Bland-Altman plots demonstrated better agreement using the semi-automated method (a range of 95% limits -0.11 to 0.10) than that in the manual method (-0.34 to 0.27). The inter-observer agreement was also good using the semi-automated method (κ = 0.866). CONCLUSIONS: The H/M ratio using the semi-automated method showed high reproducibility in both early and delayed imaging.

A novel program to accurately quantify infarction volume by (99m)Tc MIBI SPECT, and its application for re-analyzing the effect of erythropoietin administration in patients with acute myocardial infarction.

BACKGROUND: This study aimed to apply a software to calculate myocardial infarction (MI) volume by single-photon emission computed tomography. METHODS AND RESULTS: The cardioVol software has been developed to reconstruct 3D figures from sequential short axis images. We re-analyzed the data from the EPO/AMI-I Study. The MI volume at baseline correlated with maximum creatine kinase. The MI volume significantly decreased during the 6-month follow up in the erythropoietin (EPO) group, but not in the control group. The decrements of MI volume in the EPO group were significantly larger than those in the control group. CONCLUSIONS: The efficacy of EPO was further confirmed by the software.

Standardization of the heart-to-mediastinum ratio of 123I-labelled-metaiodobenzylguanidine uptake using the dual energy window method: feasibility of correction with different camera-collimator combinations.

BACKGROUND: Although the heart-to-mediastinum (H/M) ratio in a planar image has been used for practical quantification in (123)I-metaiodobenzylguanidine (MIBG) imaging, standardization of the parameter is not yet established. We hypothesized that the value of the H/M ratio could be standardized to the various camera-collimator combinations. METHODS AND RESULTS: Standard phantoms consisting of the heart and mediastinum were made. A low-energy high-resolution (LEHR) collimator and a medium-energy (ME) collimator were used. We examined multi-window correction methods with (123)I- dual-window (IDW) acquisition, and planar images were obtained with IDW correction and the LEHR collimator. The images were obtained using the following gamma camera systems: GCA 9300A (Toshiba, Tokyo), E.CAM Signature (Toshiba/Siemens, Tokyo) and Varicam (GE, Tokyo). Cardiac phantom studies demonstrated that contamination of the H/M count ratio was greater with the LEHR collimator and least with the ME collimator. The corrected H/M ratio with the LEHR collimator was similar to that with ME collimators. The uncorrected H/M ratio with the ME collimator was linearly related to the H/M ratio with IDW correction with the LEHR collimator. The relationship between the uncorrected H/M ratios determined with the LEHR (E.CAM) and the ME collimators was y = 0.56x + 0.49, where y = H/M ratio with the E.CAM and x = H/M ratio with the ME collimator. The average normal values for the low-energy collimator (n=18) were 2.2+/-0.2 (initial H/M ratio) and 2.42+/-0.2 (delayed H/M ratio), and for the low/medium-energy (LME) collimator (n=14) were 2.63+/-0.25 (initial H/M ratio) and 2.87+/-0.19 (delayed H/M ratio). H/M ratios in previous clinical studies using LEHR collimators are comparable to those with ME collimators. CONCLUSION: The IDW-corrected H/M ratios determined with the LEHR collimator were similar to those determined with the ME collimator. This finding could make it possible to standardize the H/M ratio in planar imaging among various collimators in the clinical setting.

Cytological and histological diagnoses of recurrent thyroid carcinoma with monoclonal antibody JT-95, which can detect modified fibronectin.

Although fine needle aspiration (FNA) cytology has increasingly gained importance as a tool in thyroid diagnosis over the recent years, up to 20% of thyroid carcinomas, in particular follicular tumors and follicular variant tumors, are inconclusive by FNA. The monoclonal antibody (MoAb) JT-95 detects the modified fibronectin, expressed in most thyroid carcinomas. Consequently, it has been applied to FNA and tissue section specimens obtained from thyroid tumors during surgery. For FNA specimens of 57 thyroid tumors followed-up for more than 10 years postoperatively and stained with both the Papanicolaou and the immunoperoxidase technique using MoAb JT-95, we retrospectively compared the sensitivity, specificity, and diagnostic accuracy of the two procedures. Histological specimens stained with HE and investigated by JT-95 were also re-evaluated. The pathological results of aspirated specimens, after a change in diagnosis following recurrence, revealed that 43 of 47 malignant lesions were positive, while nine of 10 benign tumors remained unreactive using MoAb JT-95. Sensitivity was 91.4%, specificity 90.0%, and diagnostic accuracy 91.2% by JT-95 cytology. By contrast, sensitivity ascertained by the Papanicolaou technique was 78.1%, specificity 100%, and accuracy 82.4%. Of the six examples that recurred during the 10-12-year follow-up period, tissue sections of all six and aspirated materials of five of the six were stained by JT-95.

Global and regional evaluation of systolic and diastolic left ventricular temporal parameters using a novel program for ECG-gated myocardial perfusion SPECT--validation by comparison with gated equilibrium radionuclide angiography and speckle-tracking radial strain from echocardiography.

BACKGROUND: A newly developed program, named cardioGRAF, enabled the evaluation of left ventricular (LV) systolic and diastolic temporal parameters for the estimation of heart failure using ECG-gated myocardial perfusion SPECT (GMPS). OBJECTIVE: The feasibility of those global (g-) and regional (r-) parameters was validated to compare with gated equilibrium radionuclide angiography (ERNA) and speckle-tracking radial strain (STS) from echocardiography. METHODS: Thirty-three patients were studied using GMPS and ERNA (n=11) or GMPS and STS (n=22). The following g- or r-parameters obtained by cardioGRAF and ERNA or STS were compared: time to end systole (TES), time from end systole to peak filling rate (TPF1), time from 0 to peak filling rate (TPF2), time to peak radial strain (TPS), time from peak strain to peak negative strain rate (TP-SR1), and time from 0 to peak negative strain rate (TP-SR2). RESULTS: All g-parameters were successfully obtained by cardioGRAF and ERNA. The results demonstrated good correlations (g-TES: r = 0.79, p < 0.005; g-TPF1: r = 0.75, p < 0.02; TPF2: r = 0.83, p < 0.005). The differences were 11.9 +/- 31.8 ms in g-TES, 19.9 +/- 65.4 ms in g-TPF1, and 37.7 +/- 67.4 ms in g-TPF2. All r-parameters were successfully obtained by cardioGRAF. Eight patients and 12 segments were excluded because of the inadequate quality of routine echocardiography for STS analysis. However, r-parameters obtained by cardioGRAF were significantly correlated with those of STS (r-TES and r-TPS: r = 0.61, p = 1 x 10(-8); r-TPF1 and r-TP-SR1: r = 0.69, p = 3 x 10(-11); r-TPF2 and r-TP-SR2: r = 0.76, p = 2 x 10(-15)). The differences were 22.1 +/- 38.2 ms between r-TES and r-TPS, 7.0 +/- 123.4 ms between r-TPF1 and r-TP-SR1, and 38.1 +/- 111.5 ms between r-TPF2 and r-TP-SR2. CONCLUSION: The feasibility of evaluating systolic and diastolic temporal parameters by a new program was validated. This program has the potential to evaluate both diastolic and systolic heterogeneous wall motions which express dyssynchrony in heart failure.

Quantification of left ventricular regional functions using ECG-gated myocardial perfusion SPECT--validation of left ventricular systolic functions--.

OBJECTIVE: We have developed a program to quantify regional left ventricular (LV) function and wall motion synchrony using ECG-gated myocardial perfusion SPECT (MPS). This preliminary study was undertaken to validate the use of this program for estimating regional LV systolic function. METHODS: Patients were subjected to MPS by 99mTc-sestamibi at rest. The study included 20 patients who were confirmed to have a low probability of coronary artery disease (LPG; low probability group), 19 heart disease patients who were examined by MPS and equilibrium radionuclide angiography (ERNA) (ERG; ERNA group), and 24 patients who were examined by MPS and 2-dimensional echocardiography (2DE) (2DEG; 2DE group). The values of the ejection fraction (EF) and peak ejection rate (PER) were estimated. The global functions evaluated by this program were compared with those obtained by ERNA in the ERG. For regional assessment, the reference values of the functional indices were obtained for 17 LV segments in LPG. The Z score, (reference average value of the segment--patient's value of the segment)/reference standard deviation of the segment, was used for the evaluation of regional functions; a score equal to or greater than 2 was defined as abnormal. Semiquantitative visual interpretation of 2DE was used as the standard to assess wall motion. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these criteria and the relationship between 2DE grading and Z scoring were validated in 2DEG. RESULTS: The values of the global EF and PER evaluated by this program correlated with those determined by ERNA (r = 0.76 and 0.58, respectively; p < 0.005 and 0.01, respectively). The sensitivities of regional EF and PER for segmental wall motion abnormalities were 86.7% and 68.7%, respectively; their specificities were 86.7% and 95.5%, respectively; their PPVs were 64.3% and 79.2%, respectively; and their NPVs were 96.0% and 91.7%, respectively. The Z scores of these indices significantly correlated with the scores determined by 2DE (rs = 0.70 and 0.68, respectively; p < 10(-10)). CONCLUSION: The potential of this program to quantify the regional systolic function was validated.