Microvascular function measurement in mice: From large to small.

There is a growing body of interest in cardiac microvascular function because it plays an important role in various cardiac disease conditions. Therefore, efforts have been made to develop non-invasive techniques to measure microvascular function. In this issue of the journal, Guerraty et al developed a micro-SPECT-based approach to assess microvascular function in in vivo mice. They applied two independent approaches to measure microvascular function: (1) myocardial blood flow measurement using 99mTc-sestamibi as a flow tracer and (2) intramyocardial blood volume measurement using 99mTc-red blood cells. Although there are issues to be addressed, they provided an important framework for non-invasive assessment of microvascular function in mice, where a number of disease models are readily available. Thus, their approaches are encouraging for facilitating better understanding of pathophysiology underlying microvascular disease models, and thereby the development of therapeutic options in future.

Feasibility of simultaneous 99mTc-tetrofosmin and 123I-BMIPP dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction.

BACKGROUND: Simultaneous dual-tracer imaging using isotopes with close photo-peaks may benefit from improved properties of cadmium-zinc-telluride (CZT)-based scanners. METHODS: Thirty patients having undergone primary percutaneous coronary intervention for acute myocardial infarction underwent single-(99mTc-tetrofosmin (TF) or 123I-BMIPP first) followed by simultaneous 99mTc-TF /123I-BMIPP dual-tracer imaging using a Discovery NM/CT 670 CZT. The values for the quantitative gated-SPECT (QGS) and the quantitative perfusion SPECT (QPS) were assessed. RESULTS: The intra-class correlation (ICC) coefficients between the single- and dual-tracer imaging were high in all the QGS and QPS data (Summed motion score: 0.95, summed thickening score: 0.94, ejection fraction: 0.98, SRS for 99mTc-TF: 0.97/ for 123I-BMIPP: 0.95). Wall motion, wall thickening and rest scores per coronary-territory-based regions were also comparable between the single- and dual imaging (ICC coefficient > 0.91). The interrater concordance in the visual analysis for the infarction and perfusion-metabolism mismatch was significant for the global and regional left ventricle (P < 0.001). CONCLUSION: The quantitative/semi-quantitative values for global and regional left-ventricular function, perfusion, and fatty acid metabolism were closely comparable between the dual-tracer imaging and the single-tracer mode. These data suggests the feasibility of the novel CZT-based scanner for the simultaneous 99mTc-TF /123I-BMIPP dual-tracer acquisitions in clinical settings.

Ultrafast bone scintigraphy scan for detecting bone metastasis using a CZT whole-body gamma camera.

PURPOSE: To evaluate the feasibility of short whole-body bone scan acquisition times using a novel gamma camera with cadmium-zinc-telluride (CZT) semiconductor detectors. METHODS: We retrospectively enrolled 78 consecutive patients with prostate cancer who underwent bone scintigraphy using a whole-body gamma camera with CZT detectors. After acquisition of list-mode data with 180 s per bed position, anterior and posterior whole-body images were reconstructed using the first 5%, 10%, 25%, 50%, 75% and 100% of the list-mode data. Two experienced nuclear medicine physicians interpreted the images, and interrater agreement and the diagnostic value of the images were determined. Quantitative artificial neural network (ANN) values, bone scan indexes (BSI) and hotspot numbers (HsN) were also calculated by automated diagnostic software. RESULTS: Excellent interrater reliabilities of the visual assessments were obtained for the 100%, 75%, 50%, and 25% images (κ = 0.88, 0.88, 0.88 and 0.88, respectively). The 5% images also showed high diagnostic value (sensitivity 0.94, specificity 0.84 and accuracy 0.86). Intraclass correlation coefficients (ICC) between the 100% images and the reduced acquisition time images were evaluated in quantitative analyses, and excellent correlations were observed for ANN value in the 75% images (ICC 0.77), for BSI in all the reduced acquisition time images (75%, 50%, 25%, 10% and 5%; ICC 0.99, 0.99, 0.99, 0.96 and 0.75, respectively), and for HsN in the 75%, 50%, 25% and 10% images (ICC 0.99, 0.99, 0.98 and 0.90, respectively). CONCLUSION: Whole-body gamma cameras with CZT detectors have the potential to reduce image acquisition times and the dose of radioisotope injected for bone scans.

How do we establish cardiac sympathetic nervous system imaging with 123I-mIBG in clinical practice? Perspectives and lessons from Japan and the US.

Cardiac denervation is associated with progressive left ventricular (LV) dysfunction, ventricular arrhythmias, and sudden cardiac death (SCD) in heart failure (HF). In this regard, it is important to evaluate cardiac-specific sympathetic nervous system (SNS) function. The radiotracer Iodine-123 meta-iodobenzylguanidine (123I-mIBG) can noninvasively evaluate pre-synaptic SNS function. Recent multicenter trials have shown 123I-mIBG to have strong predictive value for fatal arrhythmias and cardiac death in HF. 123I-mIBG was initially developed in the USA in the 1970s. In 1992, the Japanese Ministry of Health and Labour approved 123I-mIBG for the assessment of cardiac function. Following approval, the Japanese nuclear cardiology community developed 123I-mIBG imaging services in various medical centers. Japanese groups have been trying to establish the clinical utility of 123I-mIBG and standardize parameters for data acquisition and image analysis. The US Food and Drug Administration (FDA) has approved clinical use of 123I-mIBG for cardiac and non-cardiac imaging. However, clinical use of 123I-mIBG in the US has been very limited. The number of 123I-mIBG studies in Japan has also been limited. There are similarities and differences between the two countries. To establish the clinical utility of 123I-mIBG in both countries, it is important to characterize the situations of 123I-mIBG in each.

Postconditioning Accelerates Myocardial Inflammatory Resolution Demonstrated by 14C-Methionine Imaging and Attenuates Ventricular Remodeling After Ischemia and Reperfusion.

BACKGROUND: Methionine uptake after myocardial infarction has been proven to reflect myocardial inflammation. The effect of postconditioning on the post-infarction inflammatory process, however, remains to be elucidated.Methods and Results:In control (n=22) and postconditioning rats (n=23), the left coronary artery was occluded for 30 min, followed by reperfusion for 1, 3, 7, and 14 days. Postconditioning was performed immediately following the reperfusion. 14C-methinine (0.74 MBq) and 201Tl (14.8 MBq) were injected 20 and 10 min prior to sacrifice, respectively. One minute before sacrifice, 150-180 MBq of 99 mTc-MIBI was injected immediately following the re-occlusion of the left coronary artery to verify the area at risk, and left ventricular triple-tracer autoradiography was performed. To examine the ventricular remodeling, echocardiography was performed 2 months after reperfusion in both groups (n=6 each). In the control rats, the methionine uptake ratios on days 1, 3, 7, and 14 were 0.74±0.12, 1.85±0.16, 1.48±0.10, 1.25±0.04, respectively. With postconditioning, methionine uptake was similar on day 3 (1.90±0.21), but was lower on day 7 (1.23±0.22, P<0.05) and day 14 (1.08±0.09, P<0.005). Echocardiography revealed that postconditioning reduced the ventricular end-diastolic (0.97±0.16 to 0.78±0.12 cm, P<0.05) and systolic (0.85±0.21 to 0.55±0.23 cm, P<0.05) dimensions and improved ventricular percentage fractional shortening (12±6.2 to 29±12 %, P=0.01). CONCLUSIONS: 14C-methinine imaging revealed that postconditioning accelerated resolution of inflammation and attenuated ventricular remodeling.

Quantification of osteoblastic activity in epiphyseal growth plates by quantitative bone SPECT/CT.

OBJECTIVE: Quantifying the function of the epiphyseal plate is worthwhile for the management of children with growth disorders. The aim of this retrospective study was to quantify the osteoblastic activity at the epiphyseal plate using the quantitative bone SPECT/CT. MATERIALS AND METHODS: We enrolled patients under the age of 20 years who received Tc-99m hydroxymethylene diphosphonate bone scintigraphy acquired by a quantitative SPECT/CT scanner. The images were reconstructed by ordered subset conjugate-gradient minimizer, and the uptake on the distal margin of the femur was quantified by peak standardized uptake value (SUVpeak). A public database of standard body height was used to calculate growth velocities (cm/year). RESULTS: Fifteen patients (6.9-19.7 years, 9 female, 6 male) were enrolled and a total of 25 legs were analyzed. SUVpeak in the epiphyseal plate was 18.9 ± 2.4 (average ± standard deviation) in the subjects under 15 years and decreased gradually by aging. The SUVpeak correlated significantly with the age- and sex-matched growth velocity obtained from the database (R2 = 0.83, p < 0.0001). CONCLUSION: The SUV measured by quantitative bone SPECT/CT was increased at the epiphyseal plates of children under the age of 15 years in comparison with the older group, corresponding to higher osteoblastic activity. Moreover, this study suggested a correlation between growth velocity and the SUV. Although this is a small retrospective pilot study, the objective and quantitative values measured by the quantitative bone SPECT/CT has the potential to improve the management of children with growth disorder.

Quantification of bone metabolic activity in the natural course of fractural lesions measured by quantitative SPECT/CT.

Objectives: While increased uptake at the bone fractural site gradually decreases over time on bone scans, the rate of change has not been quantitatively evaluated. The purpose of this study was to quantify the extent of bone metabolic changes in fractural lesions on bone SPECT/CT. Methods: We reviewed bone scans acquired by dedicated SPECT/CT and chose those scans in which quantitative SPECT/CT of the same range was acquired twice or more. We set the region of interest on lesions of bone fracture and degeneration, and measured the maximum standardized uptake value (SUVmax). From the SUVmax of lesions and the interval between scans, a value for 30-day change in SUVmax was calculated as ∆SUVmax30d. The relationship between preSUVmax, SUVmax for the first scan of the comparison, and ∆SUVmax30d was evaluated utilizing a linear least-squares method. Furthermore, we assessed the ability to differentiate between fracture and degeneration using receiver operating characteristics (ROC) analysis and the Mann-Whitney U test. All cases were then categorized into five groups according to preSUVmax. Values of p <0.05 were considered statistically significant. Results: We investigated 175 scans from 60 patients and analyzed scan combinations for 157 fractural lesions and 266 degenerative lesions. The relationship between preSUVmax of fractural lesions and ∆SUVmax30d was approximated as ∆SUVmax30d =-0.15×preSUVmax +1.35 (R 2=0.60, p<0.0001). Area under the curves for all cases, 30≤ preSUVmax, 20≤ preSUVmax <30, 15≤ preSUVmax <20, 10≤ preSUVmax <15, and preSUVmax <10 were 0.73, 0.89, 0.86, 0.80, 0.91, and 0.59, respectively. Median ∆SUVmax30d was significantly lower at fractural lesions than at degenerative lesions (-0.62 vs -0.04; p <0.0001). As for analyses of groups divided by preSUVmax, all median ∆SUVmax30d for fractural lesions were significantly lower than those of degenerative lesions except for the group with preSUVmax <10. Conclusion: The increased uptake at the fractural bone lesion observed in the quantitative bone SPECT/CT gradually decreased at the rate of SUV 0.15 per month, which showed a different trend with degenerative change.

Atlas of non-pathological solitary or asymmetrical skeletal muscle uptake in [18F]FDG-PET.

Positron emission tomography (PET) using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is widely used in oncology and other fields. In [18F]FDG PET images, increased muscle uptake is observed owing exercise load or muscle tension, in addition to malignant tumors and inflammation. Moreover, we occasionally observe non-pathological solitary or unilateral skeletal muscle uptake, which is difficult to explain the strict reason. In most cases, we can interpret them as not having pathological significance. However, it is important to recognize such muscle uptake patterns to avoid misdiagnoses with pathological ones. Therefore, the teaching point of this pictorial essay is to comprehend the patterns of solitary or asymmetrical skeletal muscle uptake seen in routine [18F]FDG-PET scans. As an educational goal, you will be able to mention muscles where intense physiological [18F]FDG uptake can be observed, differentiate between physiological muscle uptake and lesion, and discuss with any physicians or specialists about uncertain muscle uptake.

Satisfied quantitative value can be acquired by short-time bone SPECT/CT using a whole-body cadmium-zinc-telluride gamma camera.

The aim of this study was to evaluate the quantitative values of short-time scan (STS) of metastatic lesions compared with a standard scan (SS) when acquired by whole-body bone SPECT/CT with cadmium-zinc-telluride (CZT) detectors. We retrospectively reviewed 13 patients with bone metastases from prostate cancer, who underwent SPECT/CT performed on whole-body CZT gamma cameras. STSs were obtained using 75, 50, 25, 10, and 5% of the list-mode data for SS, respectively. Regions of interest (ROIs) were set on the increased uptake areas diagnosed as metastases. Intraclass correlation coefficients (ICCs) of standardized uptake values (SUVs) for the ROIs were calculated between the SS and each STS, and ICC ≥ 0.8 was set as a perfect correlation. Moreover, the repeatability coefficient (RC) was calculated, and RC ≤ 20% was defined as acceptable. A total of 152 metastatic lesions were included in the analysis. The ICCs between the SS vs. 75%-STS, 50%-STS, 25%-STS, 10%-STS, and 5%-STS were 0.999, 0.997, 0.994, 0.983, and 0.955, respectively. The RCs of the SS vs. 75%-STS, 50%-STS, 25%-STS, 10%-STS, and 5%-STS were 7.9, 12.4, 19.8, 30.8, and 41.3%, respectively. When evaluating the quality of CZT bone SPECT/CT acquired by a standard protocol, 25%-STS may provide adequate quantitative values.

Can the function of the tubarial glands be evaluated using [99mTc]pertechnetate SPECT/CT, [18F]FDG PET/CT, and [11C]methionine PET/CT?

BACKGROUND: The tubarial glands (TGs) are recently reported as newly found salivary gland structures that can be organs at risk predominantly localized in the tori tubarius in the nasopharynx using prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT). The aims of this study were to analyze uptake in the TGs compared with that in the other salivary glands and palatine tonsils using [99mTc]pertechnetate SPECT/CT, [18F]FDG PET/CT, and [11C]methionine PET/CT and to confirm whether these three imaging modalities are useful in evaluating the physiological function of the TGs. Twelve and 130 patients, who underwent [99mTc]pertechnetate SPECT/CT and [18F]FDG/[11C]methionine PET/CT, respectively, were retrospectively included. [99mTc]pertechnetate uptake in the tori tubarius was visually assessed and semiquantitatively compared with that in the background, parotid salivary glands (PSGs), submandibular salivary glands (SmSGs), and sublingual salivary glands (SlSGs). Correlations of [18F]FDG and [11C]methionine uptakes in the tori tubarius with those in the other three salivary glands and palatine tonsils were analyzed. RESULTS: [99mTc]pertechnetate uptake in the tori tubarius was invisible and was not significantly higher than that in the background. Both [18F]FDG and [11C]methionine uptakes in the tori tubarius were correlated with that in the palatine tonsils (r = 0.56, p < 0.0001; r = 0.48, p < 0.0001, respectively). [18F]FDG uptake in the tori tubarius was not positively correlated with that in the PSGs, SmSGs, and SlSGs (r = - 0.19, p = 0.03; r = - 0.02, p = 0.81; r = 0.12, p = 0.17, respectively). [11C]methionine uptake in the tori tubarius was correlated with that in the SmSGs and SlSGs (r = 0.24, p = 0.01; r = 0.32, p < 0.01, respectively), but not with that in the PSGs (r = 0.16, p = 0.08). CONCLUSIONS: The TGs were undetectable on [99mTc]pertechnetate SPECT/CT. Both [18F]FDG and [11C]methionine uptakes in the tori tubarius were clearly affected by that in the palatine tonsils and was little related to that in the other salivary glands. Therefore, it seems difficult to evaluate the physiological function of the TGs as salivary glands using [99mTc]pertechnetate SPECT/CT, [18F]FDG PET/CT, and [11C]methionine PET/CT imaging.

Evaluation of the kappa-opioid receptor-selective tracer [(11)C]GR103545 in awake rhesus macaques.

PURPOSE: The recent development in radiosynthesis of the (11)C-carbamate function increases the potential of [(11)C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (kappa-OR) with PET. In the present study, [(11)C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. METHODS: Regional brain uptake kinetics of [(11)C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [(11)C]GR103545 was determined in cells transfected with cloned human opioid receptors. RESULTS: In vitro binding assays demonstrated a high affinity of GR103545 for kappa-OR (K(i) = 0.02 +/- 0.01 nM) with excellent selectivity over mu-OR (6 x 10(2)-fold) and) delta-OR (2 x 10(4)-fold). PET imaging revealed a volume of distribution (V(T)) pattern consistent with the known distribution of kappa-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. CONCLUSION: [(11)C]GR103545 is selective for kappa-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET.

Cardiac Amyloidosis: Current Diagnostic Strategies Using Multimodality Imaging.

Amyloidosis is a systemic disorder in which abnormal amyloid proteins deposit in body organs, leading to organ dysfunction and death. Cardiac amyloid deposition, causing a sort of restrictive cardiomyopathy and associated with increased risk of mortality. Most cases of cardiac amyloidosis are of either light chain or transthyretin type. Early and accurate diagnosis of cardiac amyloidosis may improve outcomes. However, diagnosis requires systematic approach including electrocardiography and biomarkers when encountered suspicious candidate. Diagnosis by multimodality noninvasive imaging have been substantially studied and established for differentiation from subtypes. Recent advance in the treatment of amyloidosis offers therapeutic monitoring and prognosis.

A new computerized assessment battery for cognition (C-ABC) to detect mild cognitive impairment and dementia around 5 min.

This study aimed to develop a new computerized assessment battery for cognition (C-ABC) to detect mild cognitive impairment (MCI) and dementia. We performed C-ABC in subjects with dementia (n = 422), MCI (n = 145), and normal cognition (NC; n = 574), and analyzed by age stratum (50s, 60s, and 70-85 years). To distinguish MCI from NC, the C-ABC total combined score, which were calculated by dividing the C-ABC total score by the C-ABC required time, revealed the best area under the curves (AUC) at 0.838 and 0.735 in the 50s and 60s age groups, respectively; notably, this entire procedure took approximately 5 min. To distinguish dementia from NC and MCI, the partial items of C-ABC (items 3 + 6 combined score) revealed the best AUCs at 0.910, 0.874, and 0.882 in the 50s, 60s, and 70-85 age groups, respectively. Furthermore, the items 3 + 6 combined score established the best AUC at 0.794 in the 70-85 age group to distinguish MCI from NC; this entire procedure took around 2 min. Hence, this study suggests that C-ABC could be a useful tool for detecting dementia or MCI in a short time.

High-speed scanning of planar images showing 123I-MIBG uptake using a whole-body CZT camera: a phantom and clinical study.

BACKGROUND: The heart-to-mediastinum ratio (HMR) obtained in myocardial sympathetic innervation imaging using 123I-metaiodobenzylguanidine (MIBG) is used for heart failure or Lewy body diseases (LBD). Discovery NM/CT 670 CZT, a novel whole-body scanner, enables direct HMR measurements in planar images, in contrast to cardiac-dedicated CZT-based cameras which require specific post-processing reconstruction. We sought to investigate the clinical utility of the Discovery NM/CT 670 CZT for myocardial innervation imaging and the potential time reduction. RESULTS: Following preliminary phantom examinations, 123I-MIBG planar imaging was performed in 36 patients with suspected or known LBD to measure HMRs with a collection time of 300 s. Images for different collection times were subsequently reframed using already acquired data, and changes in HMRs were evaluated. The HMRs for patients with versus without clinically diagnosed LBD were 1.63 ± 0.08 versus 2.21 ± 0.08 at early phase (p < 0.001) and 1.54 ± 0.09 versus 2.08 ± 0.09 at delayed phase (p < 0.001). The difference of HMRs (300 s - other collection time) became greater as the collection time became shorter. There was good consistency in HMRs between the 300-s images (reference) and the 200-s (intra-class correlation (ICC) coefficients > 0.99), 100-s (ICC coefficients > 0.97), and 50-s (ICC coefficients > 0.89) images. CONCLUSIONS: In planar images with a whole-body CZT-based camera, the HMRs of patients with LBD were significantly lower than those without. HMRs with the collection time of 50 s and longer showed good consistency with those of 300 s in the ICC analysis. These findings indicate a clinical utility of this novel scanner for HMR measurements and potential time reductions.

Shortened acquisition time in simultaneous 99mTc-tetrofosmin and 123I-ß-methyl-p-iodophenyl pentadecanoic acid dual-tracer imaging with cadmium-zinc-telluride detectors in patients undergoing primary coronary intervention for acute myocardial infarction.

OBJECTIVE: The use of cadmium-zinc-telluride-based scanners may increase the clinical feasibility of simultaneous dual-isotope imaging. In the current study, we sought to investigate a potential acquisition time in simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-isotope imaging using a Discovery NM/CT 670 cadmium-zinc-telluride. METHODS: Simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-isotope imaging was performed in 29 patients who had undergone primary percutaneous coronary intervention for acute myocardial infarction. Referenced images with an acquisition time of 65 s/view (16.25 min) were reframed to produce images with acquisition times of 33, 16, and 8 s/view. The values for the quantitative-gated single-photon emission computed tomography (SPECT) and the quantitative perfusion SPECT were compared. RESULTS: The quantitative-gated SPECT values for images with 33, 16, and 8 s/views showed good consistency with those for 65 s/view (the lower 95% confidence intervals for the intraclass correlation were ≥0.80). The quantitative perfusion SPECT values for Tc-tetrofosmin images with 33, 16, and 8 s/views also showed good consistency with those for 65 s/view; however, the quantitative perfusion SPECT values for I-ß-methyl-p-iodophenyl pentadecanoic acid images with an acquisition time of 8 s/view were not consistent with the reference acquisition time of 65 s/view. CONCLUSIONS: The quantitative-gated SPECT and quantitative perfusion SPECT values obtained from images with shorter acquisition times correlated with the values obtained from images with a reference acquisition time of 65 s/view; however, tracer-specific predisposition should be considered. These findings suggest that it is possible to reduce acquisition time when performing simultaneous Tc-tetrofosmin/I-ß-methyl-p-iodophenyl pentadecanoic acid dual-tracer imaging with the novel cadmium-zinc-telluride scanner.

Prediction of functional recovery after revascularization using quantitative gated myocardial perfusion SPECT: a multi-center cohort study in Japan.

BACKGROUND: Prediction of left ventricular functional recovery is important after myocardial infarction. The impact of quantitative perfusion and motion analyses with gated single-photon emission computed tomography (SPECT) on predictive ability has not been clearly defined in multi-center studies. METHODS: A total of 252 patients with recent myocardial infarction (n = 74) and old myocardial infarction (n = 175) were registered from 25 institutions. All patients underwent resting gated SPECT using (99m)Tc-hexakis-2-methoxy-isobutyl isonitrile (MIBI) and repeated the study after revascularization after an average follow-up period of 132 +/- 81 days. Visual and quantitative assessment of perfusion and wall motion were performed in 5,040 segments. RESULTS: Non-gated segmental percent uptake and end-systolic (ES) percent uptake were good predictors of wall motion recovery and significantly differed between improved and non-improved groups (66 +/- 17% and 55 +/- 18%, p < 0.0001 for non-gated; 64 +/- 16% and 51 +/- 17% for ES percent uptake, p < 0.0001). The area under the curve of receiver operating characteristics curve for non-gated percent uptake, ES percent uptake, end-diastolic percent uptake and visual perfusion defect score was 0.70, 0.71, 0.61, and 0.56, respectively. Sensitivity and specificity of percent uptake were 68% and 64% for non-gated map and 80% and 52% for ES percent uptake map. An optimal threshold for predicting segmental improvement was 63% for non-gated and 52% for ES percent uptake values. CONCLUSION: Segmental (99m)Tc-MIBI uptake provided a useful predictor of wall motion improvement. Application of quantitative approach with non-gated and ES percent uptake enhanced predictive accuracy over visual analysis particularly in a multi-center study.

Effect of sample size for normal database on diagnostic performance of brain FDG PET for the detection of Alzheimer's disease using automated image analysis.

OBJECTIVE: To investigate the relationship between the sample size for a normal database (NDB) and diagnostic performance of FDG PET using three-dimensional stereotactic surface projection for the detection of Alzheimer's disease. METHODS: We generated nine NDB sets consisting of 4, 6, 8, 10, 20, 30, 40, 50 and 60 normal subjects. In order to assess the diagnostic performance using these NDBs to distinguish Alzheimer's disease patients from normal subjects, we recruited 52 patients with probable Alzheimer's disease (25 males, 27 females; mean age, 66.8+/-8.1 years) and 50 normal subjects (24 males, 26 females; mean age, 65.7+/-9.4 years). A receiver operating characteristic (ROC) analysis was performed for comparison of diagnostic accuracy among NDB sets. RESULTS: Small NDBs (n< or =10) yielded poor quality of mean and SD images as compared with large NDBs (n> or =20). The ROC curves of the smaller group varied inconsistently, whereas those of the larger group were nearly superimposable. The area under the ROC curve (AUC) of the NDBs with sample size 6 (0.911) or 8 (0.929) was significantly smaller than that of the largest NDB (n=60, 0.956). The AUCs of the larger group did not fall below 0.950, whereas AUCs of the smaller subgroup never exceeded 0.950. CONCLUSIONS: Our data indicate that the sample size for an NDB affects the diagnostic performance of FDG PET using automated statistical approach, and that inclusion of at least 10 subjects is recommended, and 20 seems to be preferable for generating NDBs, although even a small NDB may provide clinically relevant results.

Effect of postconditioning on myocardial 99mTc-annexin-V uptake: comparison with ischemic preconditioning and caspase inhibitor treatment.

UNLABELLED: 99mTc-annexin-V imaging has been proved to be feasible to detect phosphatidylserine, which externalizes on the outer cell membrane early in the process of apoptosis. To determine whether postconditioning suppresses myocardial cell damage or apoptosis, we evaluated the intensity and distribution of 99mTc-annexin-V uptake after postconditioning in a rat model of ischemia and reperfusion and compared the effect to that of ischemic preconditioning and pretreatment with caspase inhibitor. METHODS: In control rats (n = 13), after thoracotomy the left coronary artery was occluded for 20 min followed by reperfusion for 30 or 90 min and injection of 99mTc-annexin-V (80-150 MBq). One hour later, to verify the area at risk, 201Tl (0.74 MBq) was injected intravenously just beyond the left coronary artery reocclusion, and the rats were sacrificed 1 min later. In the groups of rats with various interventions, postconditioning (n = 11) was performed just after the reperfusion, and preconditioning (n = 11) and caspase inhibitor treatment (n = 11) were performed before ischemia. Dual-tracer autoradiography was performed to assess 99mTc-annexin-V uptake and area at risk. RESULTS: In all control rats, intense 99mTc-annexin-V uptake was observed in the area at risk (uptake ratios at 30 or 90 min after reperfusion, 4.15 +/- 1.89 and 3.70 +/- 1.41, respectively). Postconditioning suppressed 99mTc-annexin-V uptake (uptake ratios at 30 or 90 min after reperfusion, 2.09 +/- 0.56, P < 0.05, and 1.88 +/- 0.69, P < 0.05, respectively). Preconditioning also suppressed uptake (uptake ratios at 30 and 90 min after reperfusion, 1.17 +/- 0.29, P < 0.005, and 1.33 +/- 0.74, P < 0.01, respectively), as did caspase inhibitor (uptake ratios at 30 and 90 min after reperfusion, 2.08 +/- 0.50, P < 0.05, and 1.27 +/- 0.24, P < 0.005, respectively). In all interventions, the percentage of cells positive on deoxyuride-5'-triphosphate biotin nick end labeling and histologic changes with myocardial cell degeneration and cell infiltrations were suppressed markedly. CONCLUSION: These data indicate that 99mTc-annexin-V imaging may be a way to monitor myocardial injury and its response to novel therapeutic interventions including postconditioning, preconditioning, and antiapoptotic therapy.

Comparison of 18F-FDG PET and optimized voxel-based morphometry for detection of Alzheimer's disease: aging effect on diagnostic performance.

UNLABELLED: The aim of this study was to compare optimized voxel-based morphometry (VBM) and (18)F-FDG PET for discrimination between patients with Alzheimer's disease (AD) and healthy subjects in relation to age. METHODS: The study population consisted of 2 groups; the first group (27 AD patients and 40 control subjects) was used to determine the locations of significant abnormalities for both PET and VBM using statistical parametric mapping, and the second group (34 AD patients and 50 control subjects) was used to compare the diagnostic performance of PET and VBM. In the second group, a z-score map for PET or VBM of each subject was obtained by comparison with the mean and SD of PET or gray-matter MR images of the control subjects. Receiver-operating-characteristic (ROC) curve analysis was then performed to compare the diagnostic performance between PET and VBM. Furthermore, group 2 was divided into the early- and late-onset subgroups, and ROC analysis was performed for each subgroup. RESULTS: In the first group, VBM revealed a significant decrease in gray-matter concentration in the hippocampus complex in AD, whereas PET showed a significant reduction in (18)F-FDG uptake in the posterior cingulate and parietotemporal lobe. The diagnostic performance of PET (0.988 +/- 0.008; mean +/- SE), as measured by the area under the ROC curve, was higher than that of VBM with (0.782 +/- 0.059) or without (0.832 +/- 0.049) modulation. PET yielded a sensitivity, specificity, and overall accuracy of 100%, 92%, and 95%, respectively, whereas for VBM the sensitivity, specificity, and accuracy were 74%, 92%, and 85%. Modulation for the VBM did not improve these values (56%, 94%, and 79%, respectively). When the early- and late-onset subjects were analyzed separately, the superiority of (18)F-FDG PET was significant only in the early-onset subgroup. CONCLUSION: The present study indicates that the detection of metabolic alteration by (18)F-FDG PET yields a better diagnostic performance for the discrimination between AD patients and healthy control subjects than does the morphologic approach by VBM, particularly in the early-onset subjects.