Organ-Specific Positron Emission Tomography Scanners for Breast Imaging: Comparison between the Performances of Prior and Novel Models.

The performances of photomultiplier tube (PMT)-based dedicated breast positron emission tomography (PET) and silicon photomultiplier tube (SiPM)-based time-of-flight (TOF) PET, which is applicable not only to breast imaging but also to head imaging, were compared using a phantom study. A cylindrical phantom containing four spheres (3-10 mm in diameter) filled with 18F-FDG at two signal-to-background ratios (SBRs), 4:1 and 8:1, was scanned. The phantom images, which were reconstructed using three-dimensional list-mode dynamic row-action maximum likelihood algorithm with various ß-values and post-smoothing filters, were visually and quantitatively compared. Visual evaluation showed that the 3 mm sphere was more clearly visualized with higher ß and smaller post-filters, while the background was noisier; SiPM-based TOF-PET was superior to PMT-based dbPET in sharpness, smoothness, and detectability, although the background was noisier at the SBR of 8:1. Quantitative evaluation revealed that the detection index (DI) and recovery coefficient (CRC) of SiPM-based TOF-PET images were higher than those of PMT-based PET images, despite a higher background coefficient of variation (CVBG). The two organ-specific PET systems showed that a 3 mm lesion in the breast could be visualized at the center of the detector, and there was less noise in the SiPM-based TOF-PET image.

Effect of radioactivity outside the field of view on image quality of dedicated breast positron emission tomography: preliminary phantom and clinical studies.

OBJECTIVE: Semi-quantitative positron emission tomography (PET) values, such as the maximum standardized uptake value (SUVmax), are widely used to identify malignant lesions and evaluate the response to treatment. The image quality of ring-shaped dedicated breast positron emission tomography (dbPET) has been known to decrease the closer it is to the detector's edge. This study aimed to investigate the effect of radioactivity (RI) outside the detector field of view (FOV) on the image quality of the ring-shaped dbPET. METHODS: A breast phantom containing the left myocardium, which was prepared using a 3D printer, filled with 18F-fluorodeoxyglucose (FDG) solution with various RI concentration ratios (RCRs) of myocardium to background and scanned with the edge of an apex positioned exactly in line with the edge of the FOV of the dbPET scanner. The phantom image quality was visually and quantitatively evaluated. Following the phantom study, left-right breast differences (the left breast uptake ratio to the right breast (LUR)) on clinical dbPET images of 74 women were quantitatively evaluated. The relationships between these parameters, clinical indices, and FDG uptake in the left myocardium on PET/computed tomography (CT) images were analyzed. RESULTS: The phantom study showed that the higher the RCR of the myocardium and the closer it is to the top edge of the phantom, the higher is the pixel value of the dbPET images. In a clinical study, LUR was significantly correlated with myocardial SUVmax (r = 0.96, p < 0.0001) and metabolic myocardial volume (r = 0.63, p = 0.001) for whole-body PET/CT imaging. Although no significant correlations were found between LUR and age (r = 0.05, p = 0.6865), body mass index (r = 0.03, p = 0.8178), or distance between the left myocardial apex and chest wall (r = 0.16, p = 0.1667). CONCLUSIONS: FDG uptake in the myocardium affected dbPET images of the left breast, especially near the chest wall. Further, the effect of RI outside the FOV, such as in the myocardium, must be considered in the quantitative evaluation of breast cancer using dbPET.

Image quality evaluation of real low-dose breast PET.

PURPOSE: To evaluate the clinical feasibility of high-resolution dedicated breast positron emission tomography (dbPET) with real low-dose 18F-2-fluorodeoxy-D-glucose (18F-FDG) by comparing images acquired with full-dose FDG. MATERIALS AND METHODS: Nine women with no history of breast cancer and previously scanned by dbPET injected with a clinical 18F-FDG dose (3 MBq/kg) were enrolled. They were injected with 50% of the clinical 18F-FDG dose and scanned with dbPET for 10 min for each breast 60 and 90 min after injection. To investigate the effect of the scan start time and acquisition time on image quality, list-mode data were divided into 1, 3, 5, and 7 min (and 10 min with 50% FDG injected) from the start of acquisition and reconstructed. The reconstructed images were visually and quantitatively compared for contrast between mammary gland and fat (contrast) and for coefficient of variation (CV) in the mammary gland. RESULTS: In visual evaluation, the contrast between the mammary gland and fat acquired at a 50% dose for 7 min was comparable and even better in smoothness than that in the images acquired at a 100% dose. No visual difference between the images with a 50% dose was found with scan start times 60 and 90 min after injection. Quantitative evaluation showed a slightly lower contrast in the image at 60 min after 50% dosing, with no difference between acquisition times. There was no difference in CV between conditions; however, smoothness decreased with shorter acquisition time in all conditions. CONCLUSIONS: The quality of dbPET images with a 50% FDG dose was high enough for clinical application. Although the optimal scan start time for improved lesion-to-background mammary gland contrast remained unknown in this study, it will be clarified in future studies of breast cancer patients.

First clinical assessment of [18F]MC225, a novel fluorine-18 labelled PET tracer for measuring functional P-glycoprotein at the blood-brain barrier.

OBJECTIVE: 5-(1-(2-[18F]fluoroethoxy))-[3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propyl]-5,6,7,8-tetrahydronaphthalen ([18F]MC225) is a selective substrate for P-glycoprotein (P-gp), possessing suitable properties for measuring overexpression of P-gp in the brain. This is the first-in-human study to examine safety, radiation dosimetry and P-gp function at the blood-brain barrier (BBB) of [18F]MC225 in healthy subjects. METHODS: [18F]MC225 biodistribution and dosimetry were determined in 3 healthy male subjects, using serial 2 h and intermittent 4 and 6 h whole-body PET scans acquired after [18F]MC225 injection. Dynamic [18F]MC225 brain PET (90 min) was obtained in 5 healthy male subjects. Arterial blood was sampled at various time intervals during scanning and the fraction of unchanged [18F]MC225 in plasma was determined. T1-weighted MRI was performed for anatomical coregistration. Total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1-TCM and 2-TCM, respectively). VT was also estimated using the Logan graphical method (Logan plot) (t* = 20 min). Surrogate parameters without blood sampling (area-under the curve [AUC] of regional time-activity curves [TACs] and negative slope of calculated TACs) were compared with the VT values. RESULTS: No serious adverse events occurred throughout the study period. Although biodistribution implied hepatobiliary excretion, secretion of radioactivity from liver to small intestine through the gallbladder was very slow. Total renal excreted radioactivity recovered during 6 h after injection was < 2%ID. Absorbed dose was the highest in the pancreas (mean ± SD, 203 ± 45 µGy/MBq) followed by the liver (83 ± 11 µGy/MBq). Mean effective dose with and without urination was 17 ± 1 µSv/MBq. [18F]MC225 readily entered the brain, distributing homogeneously in grey matter regions. 2-TCM provided lower Akaike information criterion scores than did 1-TCM. VT estimated by Logan plot was well correlated with that of 2-TCM (r2 > 0.9). AUCs of TACs were positively correlated with VT (2-TCM) values (r2: AUC0-60 min = 0.61, AUC0-30 min = 0.62, AUC30-60 min = 0.59, p < 0.0001). Negative slope of SUV TACs was negatively correlated with VT (2-TCM) values (r2 = 0.53, p < 0.0001). CONCLUSIONS: This initial evaluation indicated that [18F]MC225 is a suitable and safe PET tracer for measuring P-gp function at the BBB.

Optimal relaxation parameters of dynamic row-action maximum likelihood algorithm and post-smoothing filter for image reconstruction of dedicated breast PET.

OBJECTIVE: This study aimed to determine the optimal ß value of the relaxation control parameter and the post-smoothing filter in the list-mode dynamic row-action maximum likelihood algorithm (LM-DRAMA) to detect early stage breast cancer with high-resolution dedicated breast positron emission tomography (dbPET) in phantom and clinical studies. METHODS: A breast phantom containing four spheres (5, 7.5, 10, and 16 mm in diameter) was filled with 18F-fluorodeoxyglucose solution (sphere-to-background ratio, 8:1) and scanned on a dbPET scanner. The images were reconstructed using LM-DRAMA with different ß values (5, 20, or 100) and Gaussian post-filters (0, 0.78, 1.17, 1.56, 1.95, or 2.34 mm). Other conditions were according to those routinely used (1 iteration and 128 subsets including attenuation and scatter correction). Image quality was evaluated visually and by computing the coefficient of variation of the background (CVBG), detectability index (DI), and contrast recovery coefficient. Parameters optimized in these phantom studies were applied to 25 clinical data sets. Variabilities for different reconstruction methods in visual scores, the maximum standardized uptake value of breast cancer, and the tumor-to-background uptake ratio were estimated. RESULTS: The reconstruction images of the phantom with higher ß values and smaller post-filters yielded higher visual scores for detectability and DI and lower smoothness and CVBG scores. Based on the phantom study, the ß values and post-filter were optimized for clinical dbPET images except for ß5 and 2.34 mm post-filter. Applying the other reconstructions to clinical studies showed that ß100 provided higher quantitative parameter values. The detectability of lesions was similar for ß100 and ß20 and decreased with larger post-filters. The lesion detection rate was similar for ß100 and ß20 and decreased with larger post-filter. CONCLUSION: The relaxation coefficient factor ß20 and a 0.78- or 1.17-mm post-filter were optimal for dbPET image reconstruction with balanced spatial resolution and noise. However, they should be selected according to the impact on the dbPET image and the purpose of the examination.

Evaluation of image quality at the detector's edge of dedicated breast positron emission tomography.

BACKGROUND: Using phantoms and clinical studies in prone hanging breast imaging, we assessed the image quality of a commercially available dedicated breast PET (dbPET) at the detector's edge, where mammary glands near the chest wall are located. These are compared to supine PET/CT breast images of the same clinical subjects. METHODS: A breast phantom with four spheres (16-, 10-, 7.5-, and 5-mm diameter) was filled with 18F-fluorodeoxyglucose solution (sphere-to-background activity concentration ratio, 8:1). The spheres occupied five different positions from the top edge to the centre of the detector and were scanned for 5 min in each position. Reconstructed images were visually evaluated, and the contrast-to-noise ratio (CNR), contrast recovery coefficient (CRC) for all spheres, and coefficient of variation of the background (CVB) were calculated. Subsequently, clinical images obtained with standard supine PET/CT and prone dbPET were retrospectively analysed. Tumour-to-background ratios (TBRs) between breast cancer near the chest wall (close to the detector's edge; peripheral group) and at other locations (non-peripheral group) were compared. The TBR of each lesion was compared between dbPET and PET/CT. RESULTS: Closer to the detector's edge, the CNR and CRC of all spheres decreased while the CVB increased in the phantom study. The disadvantages of this placement were visually confirmed. Regarding clinical images, TBR of dbPET was significantly higher than that of PET/CT in both the peripheral (12.38 ± 6.41 vs 6.73 ± 3.5, p = 0.0006) and non-peripheral (12.44 ± 5.94 vs 7.71 ± 7.1, p = 0.0183) groups. There was no significant difference in TBR of dbPET between the peripheral and non-peripheral groups. CONCLUSION: The phantom study revealed poorer image quality at < 2-cm distance from the detector's edge than at other more central parts. In clinical studies, however, the visibility of breast lesions with dbPET was the same regardless of the lesion position, and it was higher than that in PET/CT. dbPET has a great potential for detecting breast lesions near the chest wall if they are at least 2 cm from the edge of the FOV, even in young women with small breasts.

References Values for Left Atrial Volumes, Emptying Fractions, Strains, and Strain Rates and Their Determinants by Age, Gender, and Ethnicity: The Multiethnic Study of Atherosclerosis (MESA).

RATIONALE AND OBJECTIVES: Left Atrial (LA) adverse remodeling is an important predictor of morbidity and mortality in several cardiovascular (CV) diseases. Our goals were to quantify and provide reference ranges for LA structure and function using feature tracking cine cardiac magnetic resonance. MATERIALS AND METHODS: 2526 participants of the Multiethnic Study of Atherosclerosis study who had feature tracking cine cardiac magnetic resonance derived LA data and were free of atrial fibrillation/flutter and prior CV events at year five follow-up examination (2010-2012) were included in this study. LA phasic indexed volumes: maximum (LAVi max), minimum (LAVi min), and preatrial contraction (LAVi preA); LA empty fractions: total, passive, and active (LAtEF, LApEF, and LAaEF); LA longitudinal strain: maximum and preatrial contraction (S max and S preA); and LA longitudinal strain rate: systolic (SR max) and early/late diastolic (SR e and SR a) were measured. Age, gender, and race/ethnicity-specific reference ranges were identified. Also, reference values in a select subgroup of healthy participants free of traditional CV risk factors at the time of exam date were reported. RESULTS: The mean ± SD for LAVi max, LAVi min, LAVi preA, S max, SR e, and SR a were in the 45-65-year-old participants: (33.8 ± 10 mL/m2), (14.5 ± 6.4 mL/m2), (24.8 ± 8.2 mL/m2), (34.6 ± 13.8 %), (-1.4 ± 0.7 s-1), (-2.1 ± 1 s-1) and in the ≥ 65-year-old participants: (35 ± 11.5 mL/m2), (16.6 ± 8.3 mL/m2), (27.6 ± 9.9 mL/m2), (31.2 ± 14.3 %), (-1 ± 0.6 s-1), (-2.1 ± 1 s-1) respectively. Younger individuals had Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smaller LA volumes and better LA function compared to their older counterparts. Similar findings were observed in Chinese-Americans as compared to Whites. CONCLUSION: This study provides reference values of LA structure and function parameters from a healthy multiethnic community-based population aged 53-94 years evaluated by FTMRI.

Bone Scintigraphy in Pembrolizumab-Induced Inflammatory Arthritis.

We present a novel report on the use of bone scintigraphy in pembrolizumab-induced inflammatory arthritis. A 70-year-old man with lung cancer complained about arthralgia after 7 courses of the pembrolizumab therapy. Tc-HMDP bone scintigraphy revealed symmetrically strong uptakes in the major distal joints of the upper and lower extremities, thereby clearly identifying them as the affected joints. The pattern of uptakes was not consistent with that of other pathophysiologies including bone metastases, hypertrophic osteoarthropathy, and rheumatoid arthritis. Tc-HMDP bone scintigraphy is more practical and cost-effective compared with PET to reveal the affected joints in pembrolizumab-induced inflammatory arthritis.

Comparison of dedicated breast positron emission tomography and whole-body positron emission tomography/computed tomography images: a common phantom study.

OBJECTIVE: High-resolution dedicated breast positron emission tomography (dbPET) can visualize breast cancer more clearly than whole-body PET/computed tomography (CT). In Japan, the combined use of dbPET and whole-body PET/CT is necessary in indications for health insurance. Although several clinical studies have compared both devices, a physical evaluation by the phantom test has not been reported. The aim of this study was to compare the ability of ring-shaped dbPET and whole-body PET/CT using a common phantom with reference to the Japanese guideline for the oncology 18F-fluorodeoxyglucose (FDG)-PET/CT data acquisition protocol. METHODS: A cylindrical breast phantom with four spheres of different diameters (16, 10, 7.5, and 5 mm) filled an FDG solution at sphere-to-background radioactivity ratios (SBRs) of 2:1, 4:1, and 8:1 was prepared. Images were then acquired by whole-body PET/CT and subsequently by dbPET. The reconstructed images were visually evaluated and the coefficient of variation and uniformity of the background (CVbackground and SDΔSUVmean), percentages of contrast and background variability (%QH,5mm and %N5mm), and their ratio (%QH,5mm/N5mm), and relative recovery coefficient were compared with the standards defined in the protocol for whole-body PET/CT. RESULTS: The parameters were calculated at an SBR of 8:1, which was the only SBR in which a 5-mm sphere was visible on both devices. The standards were defined as < 10% for CVbackground, ≤ 0.025 for SDΔSUVmean, < 5.6% for %N5mm, > 2.8 for %QH,5mm/N5mm, and > 0.38 for the relative recovery coefficient of the smallest sphere (10 mm in diameter) in the protocol for whole-body PET/CT (the %QH,5mm was not determined for that protocol); the respective values were 6.14%, 0.024, 4.55%, 3.66, and 0.33 for dbPET and 2.21%, 0.021, 3.11%, 1.72, and 0.18 for PET/CT. The QH,5mm was 16.67% for dbPET and 5.34% for PET/CT. The human images also showed higher lesion-to-background contrast on dbPET than on PET/CT despite the noisier background observed with dbPET. CONCLUSION: The common phantom study showed that the background was noisier and that the contrast was much higher in the dbPET image than in the PET/CT image. The acquisition protocol and standards for dbPET will need to be different from those used for whole-body PET/CT.

Metabolic Network Topology of Alzheimer's Disease and Dementia with Lewy Bodies Generated Using Fluorodeoxyglucose Positron Emission Tomography.

BACKGROUND: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are often misdiagnosed with each other because of similar symptoms including progressive memory loss. The metabolic network topology that describes inter-regional metabolic connections can be generated using fluorodeoxyglucose positron emission tomography (FDG-PET) data with the graph-theoretical method. We hypothesized that different metabolic connectivity underlies the symptoms of AD patients, DLB patients, and cognitively normal (CN) individuals. OBJECTIVE: This study aimed to generate metabolic connectivity using FDG-PET data and assess the network topology to differentiate AD patients, DLB patients, and CN individuals. METHODS: This study included 45 AD patients, 18 DLB patients, and 142 CN controls. We analyzed FDG-PET data using the graph-theoretical method and generated the network topology in AD patients, DLB patients, and CN individuals. We statistically assessed the topology with global and nodal parameters. RESULTS: The whole metabolic network was preserved in CN; however, diffusely decreased connection was found in AD and partially but more deeply decreased connection was observed in DLB. The metabolic topology revealed that the right posterior cingulate and the left transverse temporal gyrus were significantly different between AD and DLB. CONCLUSION: The present findings indicate that metabolic connectivity decreased in both AD and DLB, compared with CN. DLB was characterized restricted but deeper stereotyped network disruption compared with AD. The right posterior cingulate and the left transverse temporal gyrus are significant regions in the metabolic connectivity for differentiating AD from DLB.

Left Atrial Mechanical Function and Incident Ischemic Cerebrovascular Events Independent of AF: Insights From the MESA Study.

OBJECTIVES: This study sought to assess the association of baseline left atrial (LA) phasic function measured with cardia magnetic resonance (CMR) and incident ischemic cerebrovascular events (CVE). BACKGROUND: LA remodeling is a known predictor of atrial fibrillation (AF), which is a risk factor for ischemic CVE. Despite studies showing an association between LA remodeling and ischemic CVE, the association of LA mechanical function with ischemic CVE in a population free of known cardiovascular disease is not fully studied. METHODS: Phasic LA volumes; total, passive, and active LA emptying fractions (LAEF); and peak longitudinal LA strain were measured using feature-tracking CMR in 4,261 MESA (Multi-Ethnic Study of Atherosclerosis) participants (61 ± 10 years of age; 48% male). All individuals were free of clinical cardiovascular disease at baseline. Participants were followed for 11.6 ± 3.5 years for the diagnosis of incident ischemic CVE, defined as ischemic stroke or transient ischemic attack adjudicated by vascular neurologists. RESULTS: During the follow-up, 193 (1.26 per 1,000 person-years) ischemic CVE (134 ischemic strokes and 59 TIAs) occurred. Individuals with incident ischemic CVE had larger LA volumes and lower passive, active, and total LAEFs at baseline. In multivariate analysis adjusted for known CVE risk factors, left ventricular mass and interim AF, total LAEF was associated with incident ischemic CVE (hazard ratio [HR]: 0.85 per SD; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.027). The unadjusted HR for the lowest tertile of total LAEF compared to the highest tertile was 2.0 (95% CI: 1.43 to 2.79; p < 0.001), and the adjusted HR was 1.47 (95% CI: 1.04 to 2.05; p = 0.031). Addition of total LAEF to known clinical risk factors of CVE and left ventricular mass resulted in an improved predictive accuracy (C statistic of 0.76 vs. 0.73, respectively; p = 0.039). CONCLUSIONS: Reduced total LAEF was associated with incident ischemic CVE independent of known cerebrovascular risk factors and incident AF. Assessment of LA function may add further information in stratifying asymptomatic individuals at risk for ischemic stroke.

Assessment of safety, efficacy, and dosimetry of a novel 18-kDa translocator protein ligand, [11C]CB184, in healthy human volunteers.

BACKGROUND: N,N-di-n-propyl-2-[2-(4-[11C]methoxyphenyl)-6,8-dichloroimidazol[1,2-a]pyridine-3-yl]acetamide ([11C]CB184) is a novel selective radioligand for the 18-kD translocator protein (TSPO), which is upregulated in activated microglia in the brain, and may be useful in positron emission tomography (PET). We examined the safety, radiation dosimetry, and initial brain imaging with [11C]CB184 in healthy human volunteers. RESULTS: Dynamic [11C]CB184 PET scans (90 min) were performed in five healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined with high-performance liquid chromatography. No serious adverse events occurred in any of the subjects throughout the study period. [11C]CB184 was metabolized in the periphery: 36.7% ± 5.7% of the radioactivity in plasma was detected as the unchanged form after 60 min. The total distribution volume (V T) was estimated with a two-tissue compartment model. The V T of [11C]CB184 was highest in the thalamus (5.1 ± 0.4), followed by the cerebellar cortex (4.4 ± 0.2), and others. Although regional differences were small, the observed [11C]CB184 binding pattern was consistent with the TSPO distribution in the normal human brain. Radiation dosimetry was determined in three healthy male subjects using a serial whole-body PET scan acquired over 2 h after [11C]CB184 injection. [11C]CB184 PET demonstrated high uptake in the gallbladder at a later time (>60 min). In urine obtained approximately 100 min post-injection, 0.3% of the total injected radioactivity was recovered, indicating hepatobiliary excretion of radioactivity. The absorbed dose (µGy/MBq) was highest in the kidneys (21.0 ± 0.5) followed by the lungs (16.8 ± 2.7), spleen (16.6 ± 6.6), and pancreas (16.5 ± 2.2). The estimated effective dose for [11C]CB184 was 5.9 ± 0.6 µSv/MBq. CONCLUSIONS: This initial evaluation indicated that [11C]CB184 is feasible for imaging of TSPO in the brain.

Initial Evaluation of an Adenosine A2A Receptor Ligand, 11C-Preladenant, in Healthy Human Subjects.

11C-preladenant is a selective antagonist for mapping of cerebral adenosine A2A receptors (A2ARs) by PET. This is a first-in-human study to examine the safety, radiation dosimetry, and brain imaging of 11C-preladenant in healthy human subjects. Methods: Dynamic 11C-preladenant PET scans (90 min) were obtained in 5 healthy male subjects. During the scan, arterial blood was sampled at various time intervals, and the fraction of the parent compound in plasma was determined. For anatomic coregistration, T1-weighted MRI was performed. The total distribution volume (VT) was estimated using 1- and 2-tissue-compartment models (1T and 2T, respectively). The distribution volume ratio (DVR) was calculated from VT of target and reference region and obtained with a noninvasive Logan graphical reference tissue method (t* = 30 min). The applicability of a shortened protocol as an alternative to the 90-min PET scan was investigated. Tracer biodistribution and dosimetry were determined in 3 healthy male subjects, using serial whole-body PET scans acquired over 2 h after 11C-preladenant injection. Results: There were no serious adverse events in any of the subjects throughout the study period. 11C-preladenat readily entered the brain, with a peak uptake in the putamen and head of the caudate nucleus 30-40 min after tracer injection. Other brain regions showed rapid clearance of radioactivity. The regional distribution of 11C-preladenant was consistent with known A2AR densities in the brain. At pseudoequilibrium (reached at 40 min after injection), stable target-to-cerebellar cortex ratios of around 3.8-10.0 were obtained. The 2T fit better than the 1T in the low-density A2AR regions. In contrast, there were no significant differences between 1T and 2T in the high-A2AR-density regions. DVRs in the putamen and head of the caudate nucleus were around 3.8-10.3 when estimated using a Logan graphical reference tissue method with cerebellum as the reference region. PET scanning at 50 or 70 min can provide the stable DVR estimates within 10% or 5% differences at most, respectively. The radioactivity was mainly excreted through the hepatobiliary system after 11C-preladenant injection. As a result, the absorbed dose (µGy/MBq) was highest in the gallbladder wall (mean ± SD, 17.0 ± 2.5) and liver (11.7 ± 2.1). The estimated effective dose for 11C-preladenant was 3.7 ± 0.4 µSv/MBq. Conclusion: This initial evaluation indicated that 11C-preladenat is suitable for imaging of A2ARs in the brain.

Glucose Hypometabolism in Developmental Venous Anomaly Without Apparent Parenchymal Damage.

Two cases of F-FDG PET in developmental venous anomaly (DVA) with visual impairment were examined. Plain MRI could not determine the cause of visual symptoms; a contrast-enhanced CT scan showed the existence of DVA without apparent parenchymal damage due to infarction or hemorrhage. F-FDG PET revealed that the hypometabolic area extended to the visual tract, thus explaining the association between the visual impairment and DVA. F-FDG PET is therefore a useful tool for the evaluation of symptomatic DVA.

Allergin-1 inhibits TLR2-mediated mast cell activation and suppresses dermatitis.

TLR2 recognizes cell wall components of Staphylococcus aureus, which colonizes >90% of atopic eczematous skin lesions. The regulatory mechanisms of TLR2 signaling in the skin remain unclear. Allergin-1, an inhibitory immunoglobulin-like receptor containing an ITIM, is expressed on mast cells (MCs) and inhibits IgE-mediated anaphylaxis in mice. Here, we show that Allergin-1 inhibits TLR2-mediated activation of, and inflammatory cytokine production by, MCs in vitro Compared with wild-type mice, Allergin-1-deficient mice showed enhanced ear swelling with enhanced collagen deposition and greater Ly6G+ neutrophil recruitment after intra-dermal injection of Pam2CSK4 into pinnae. Using Mas-TRECK mice, which is an MC deletion system based on il4 enhancer elements, we also demonstrated that Allergin-1 on MCs is responsible for the Pam2CSK4-induced ear swelling. These results suggest that Allergin-1 on skin MCs suppresses TLR2-induced dermatitis.

Clinical application of an automatic slice-alignment method for cardiac MR imaging.

PURPOSE: We evaluated the usefulness of an automatic slice-alignment method to simplify planning of cardiac magnetic resonance (MR) scans with a 3-tesla scanner. METHODS: We obtained 2-dimensional (2D) axial multislice images using steady-state free precession (SSFP) sequences covering the whole heart at the end-diastole phase with electrocardiography (ECG) gating in 38 patients. We detected several anatomical feature points of the heart and calculated all planes required for cardiac imaging based on those points. We visually evaluated the acceptability of an acquired imaging plane and measured the angular differences of each view between the results obtained by this method and by a conventional manual pointing approach. RESULTS: The average visual scores were 3.4 ± 1.0 for short-axis images, 3.2 ± 0.9 for 4-chamber images, 3.2 ± 0.8 for 2-chamber images, and 3.3 ± 0.8 for 3-chamber images; average angular differences were 5.8 ± 5.1 (short axis), 7.7 ± 5.7 (4-chamber), 11.5 ± 6.7 (2-chamber), and 9.1 ± 4.6 degrees (3-chamber). Processing time was within 1.8 s in all subjects. CONCLUSION: The proposed method can provide planes within the clinically acceptable range and within a short time in cardiac imaging of patients with various cardiac shapes and diseases without the need for high level operator proficiency in performing the examination and interpreting results.

Multi-ethnic study of atherosclerosis: association between left atrial function using tissue tracking from cine MR imaging and myocardial fibrosis.

PURPOSE: To investigate the association between left atrial ( LA left atrium ) function and left ventricular myocardial fibrosis using cardiac magnetic resonance (MR) imaging in a multi-ethnic population. MATERIALS AND METHODS: For this HIPAA-compliant study, the institutional review board at each participating center approved the study protocol, and all participants provided informed consent. Of 2839 participants who had undergone cardiac MR in 2010-2012, 143 participants with myocardial scar determined with late gadolinium enhancement and 286 age-, sex-, and ethnicity-matched control participants were identified. LA left atrium volume, strain, and strain rate were analyzed by using multimodality tissue tracking from cine MR imaging. T1 mapping was applied to assess diffuse myocardial fibrosis. The association between LA left atrium parameters and myocardial fibrosis was evaluated with the Student t test and multivariable regression analysis. RESULTS: The scar group had significantly higher minimum LA left atrium volume than the control group (mean, 22.0 ± 10.5 [standard deviation] vs 19.0 ± 7.8, P = .002) and lower LA left atrium ejection fraction (45.9 ± 10.7 vs 51.3 ± 8.7, P < .001), maximal LA left atrium strain ( Smax maximum LA strain ) (25.4 ± 10.7 vs 30.6 ± 10.6, P < .001) and maximum LA left atrium strain rate ( SRmax maximum LA strain rate ) (1.08 ± 0.45 vs 1.29 ± 0.51, P < .001), and lower absolute LA left atrium strain rate at early diastolic peak ( SRE LA strain rate at early diastolic peak ) (-0.77 ± 0.42 vs -1.01 ± 0.48, P < .001) and LA left atrium strain rate at atrial contraction peak ( SRA LA strain rate at atrial contraction peak ) (-1.50 ± 0.62 vs -1.78 ± 0.69, P < .001) than the control group. T1 time 12 minutes after contrast material injection was significantly associated with Smax maximum LA strain (ß coefficient = 0.043, P = .013), SRmax maximum LA strain rate (ß coefficient = 0.0025, P = .001), SRE LA strain rate at early diastolic peak (ß coefficient = -0.0016, P = .027), and SRA LA strain rate at atrial contraction peak LA strain rate at atrial contraction peak (ß coefficient -0.0028, P = .01) in the regression model. T1 time 25 minutes after contrast material injection was significantly associated with SRmax maximum LA strain rate (ß coefficient = 0.0019, P = .016) and SRA LA strain rate at atrial contraction peak (ß coefficient = -0.0022, P = .034). CONCLUSION: Reduced LA left atrium regional and global function are related to both replacement and diffuse myocardial fibrosis processes. Clinical trial registration no.: NCT00005487

Expression and function of Allergin-1 on human primary mast cells.

Mast cells (MC) play an important role in allergic and non-allergic immune responses. Activation of human MC is modulated by several cell surface inhibitory receptors, including recently identified Allergin-1 expressed on both human and mouse MC. Although Allergin-1 suppresses IgE-mediated, mast cell-dependent anaphylaxis in mice, the expression profile and function of Allergin-1 on human primary MC remains undetermined. Here, we established a seven-color flow cytometry method for assessing expression and function of a very small number of human primary MC. We show that Allergin-1S1, a splicing isoform of Allergin-1, is predominantly expressed on human primary MC in both bronchoalveolar lavage (BAL) fluid and nasal scratching specimens. Moreover, Allergin-1S1 inhibits IgE-mediated activation from human primary MC in BAL fluid. These results indicate that Allergin-1 on human primary MC exhibits similar characteristics as mouse Allergin-1 in the expression profile and function.

Suppressive effects of a novel CC chemokine receptor 4 antagonist on Th2 cell trafficking in ligand- and antigen-induced mouse models.

CC chemokine receptor 4 (CCR4) has been implicated as a preferential marker for T helper type 2 (Th2) cells, and is believed to be involved in the pathology of allergic diseases by controlling Th2 cell trafficking into inflamed tissues. The objective of the study was to characterize the pharmacological properties of E0001-163, a novel CCR4 antagonist. E0001-163 was tested in both in vitro chemotaxis assays as well as in vivo mouse models of CCR4 ligand-induced air pouch and antigen-induced airway inflammation by utilizing in vitro-polarized Th2 cells. In vitro, E0001-163 inhibited migratory response of human Th2-polarized cells to CCL22, a CCR4 ligand, with an IC50 value of 11.9 nM. E0001-163 significantly suppressed CCL22-induced Th2 cell trafficking into mouse air pouch in a dose-dependent manner at doses of 3 and 10mg/kg, suggesting that E0001-163 has an inhibitory effect on CCR4-mediated T cell trafficking in vivo. In addition, E0001-163 partially decreased Th2 cell trafficking and the level of IL-4 in the lungs in Th2-tansferred and ovalbumin (OVA)-challenged mice. T cell trafficking involves multiple chemokine receptors both in acute and chronic phases, and our findings suggest that CCR4, together with other chemokine receptors, may be involved in Th2 cell trafficking under disease conditions.

Postoperative evaluation of superficial temporal artery-middle cerebral artery bypass using an MR angiography technique with combined white-blood and black-blood sequences.

PURPOSE: To assess the performance of the hybrid of opposite-contrast MR angiography (HOP MRA) technique, which combines flow dephasing and compensating sequences, in the postoperative evaluation of superficial temporal artery (STA)-middle cerebral artery (MCA) bypass. MATERIALS AND METHODS: Both 3D-HOP MRA and 3D-time-of-flight (TOF) MRA at 1.5 Tesla were performed in 19 patients after STA-MCA bypass. The two techniques were visually evaluated to compare the visualization of distal MCA branches and the length and number of depicted recipient MCA branches. Additionally, for the depicted recipient MCA branches, the contrast-to-noise ratio (CNR) and length were compared between the two techniques. RESULTS: The 3D-HOP MRA provided better visualization of the recipient MCA branches than 3D-TOF MRA in 10 of the 19 patients, while the depicted recipient MCA branches were longer on 3D-HOP MRA than on 3D-TOF MRA in 9 patients. Although not statistically significant, the average number of depicted recipient branches by 3D-HOP MRA (2.16) was greater than that by 3D-TOF MRA (1.79). 3D-HOP MRA was significantly superior to 3D-TOF MRA in both CNR (119.0 versus 74.3) and length of the recipient MCA branches (72.0 versus 49.9 pixels). CONCLUSION: 3D-HOP MRA is superior to 3D-TOF MRA for the detailed evaluation of STA-MCA bypass.