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Colloidal quantum dots (QDs) exhibit important photophysical properties, such as long-range energy diffusion, miniband formation, and collective photoluminescence, when aggregated into well-defined superstructures, such as three-dimensional (3D) and two-dimensional (2D) superlattices. However, the construction of one-dimensional (1D) QD superstructures, which have a simpler arrangement, is challenging; therefore, the photophysical properties of 1D-arranged QDs have not been studied previously. Herein, we report a versatile strategy to obtain 1D-arranged QDs using a supramolecular polymer (SP) template. The SP is composed of self-assembling cholesterol derivatives containing two amide groups for hydrogen bonding and a carboxyl group as an adhesion moiety on the QDs. Upon mixing the SP and dispersed QDs in low-polarity solvents, the QDs self-adhered to the SP and self-arranged into 1D superstructures through van der Waals interactions between the surface organic ligands of the QDs, as confirmed by transmission electron microscopy. Furthermore, we revealed efficient photoinduced fluorescence resonance energy transfer between the 1D-arranged QDs by an in-depth analysis of the emission spectra and decay curves.

The CCCTC-binding factor (CTCF) works together with the cohesin complex to drive the formation of chromatin loops and topologically associating domains, but its role in gene regulation has not been fully defined. Here, we investigated the effects of acute CTCF loss on chromatin architecture and transcriptional programs in mouse embryonic stem cells undergoing differentiation to neural precursor cells. We identified CTCF-dependent enhancer-promoter contacts genome-wide and found that they disproportionately affect genes that are bound by CTCF at the promoter and are dependent on long-distance enhancers. Disruption of promoter-proximal CTCF binding reduced both long-range enhancer-promoter contacts and transcription, which were restored by artificial tethering of CTCF to the promoter. Promoter-proximal CTCF binding is correlated with the transcription of over 2,000 genes across a diverse set of adult tissues. Taken together, the results of our study show that CTCF binding to promoters may promote long-distance enhancer-dependent transcription at specific genes in diverse cell types.

The CCCTC-binding factor (CTCF) works together with the cohesin complex to drive the formation of chromatin loops and topologically associating domains, but its role in gene regulation has not been fully defined. Here, we investigated the effects of acute CTCF loss on chromatin architecture and transcriptional programs in mouse embryonic stem cells undergoing differentiation to neural precursor cells. We identified CTCF-dependent enhancer-promoter contacts genome-wide and found that they disproportionately affect genes that are bound by CTCF at the promoter and are dependent on long-distance enhancers. Disruption of promoter-proximal CTCF binding reduced both long-range enhancer-promoter contacts and transcription, which were restored by artificial tethering of CTCF to the promoter. Promoter-proximal CTCF binding is correlated with the transcription of over 2,000 genes across a diverse set of adult tissues. Taken together, the results of our study show that CTCF binding to promoters may promote long-distance enhancer-dependent transcription at specific genes in diverse cell types.

The CCCTC-binding factor (CTCF) works together with the cohesin complex to drive the formation of chromatin loops and topologically associating domains, but its role in gene regulation has not been fully defined. Here, we investigated the effects of acute CTCF loss on chromatin architecture and transcriptional programs in mouse embryonic stem cells undergoing differentiation to neural precursor cells. We identified CTCF-dependent enhancer-promoter contacts genome-wide and found that they disproportionately affect genes that are bound by CTCF at the promoter and are dependent on long-distance enhancers. Disruption of promoter-proximal CTCF binding reduced both long-range enhancer-promoter contacts and transcription, which were restored by artificial tethering of CTCF to the promoter. Promoter-proximal CTCF binding is correlated with the transcription of over 2,000 genes across a diverse set of adult tissues. Taken together, the results of our study show that CTCF binding to promoters may promote long-distance enhancer-dependent transcription at specific genes in diverse cell types.

A scarcity of functionally validated enhancers in the human genome presents a significant hurdle to understanding how these cis-regulatory elements contribute to human diseases. We carry out highly multiplexed CRISPR-based perturbation and sequencing to identify enhancers required for cell proliferation and fitness in 10 human cancer cell lines. Our results suggest that the cell fitness enhancers, unlike their target genes, display high cell-type specificity of chromatin features. They typically adopt a modular structure, comprised of activating elements enriched for motifs of oncogenic transcription factors, surrounded by repressive elements enriched for motifs recognized by transcription factors with tumor suppressor functions. We further identify cell fitness enhancers that are selectively accessible in clinical tumor samples, and the levels of chromatin accessibility are associated with patient survival. These results reveal functional enhancers across multiple cancer cell lines, characterize their context-dependent chromatin organization, and yield insights into altered transcription programs in cancer cells.

The mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical and subcortical structures1. Recent surveys of mouse and human brains with single-cell transcriptomics2-6 and high-throughput imaging technologies7,8 have uncovered hundreds of neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for the unique identity and function of each cell type remain unknown. Here we probe the accessible chromatin in more than 800,000 individual nuclei from 45 regions that span the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to map the state of 491,818 candidate cis-regulatory DNA elements in 160 distinct cell types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences associated with the regional specificity within these cell types. We further link a considerable fraction of the cis-regulatory elements to putative target genes expressed in diverse cerebral cell types and predict transcriptional regulators that are involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of noncoding risk variants associated with various neurological diseases and traits in humans.

The mammalian cerebrum performs high-level sensory perception, motor control and cognitive functions through highly specialized cortical and subcortical structures1. Recent surveys of mouse and human brains with single-cell transcriptomics2-6 and high-throughput imaging technologies7,8 have uncovered hundreds of neural cell types distributed in different brain regions, but the transcriptional regulatory programs that are responsible for the unique identity and function of each cell type remain unknown. Here we probe the accessible chromatin in more than 800,000 individual nuclei from 45 regions that span the adult mouse isocortex, olfactory bulb, hippocampus and cerebral nuclei, and use the resulting data to map the state of 491,818 candidate cis-regulatory DNA elements in 160 distinct cell types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences associated with the regional specificity within these cell types. We further link a considerable fraction of the cis-regulatory elements to putative target genes expressed in diverse cerebral cell types and predict transcriptional regulators that are involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of noncoding risk variants associated with various neurological diseases and traits in humans.

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues.

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues.

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues.

Ag+ ions were intercalated into the transition-metal dichalcogenide TaS2 using the recently developed method of proton-driven ion introduction. Single-crystalline Ag0.58TaS2 with a stage 1 structure and Ag0.21TaS2 with a stage 2 structure were prepared using this method. The stage 2 structure of Ag0.21TaS2 was formed by exploiting the differences in ion diffusion properties among the polytypes of TaS2. Furthermore, our intercalation method can forcibly insert Ag+ ions into interlayers by applying a high voltage at low temperature (100 degrees C), resulting in the formation of thermodynamically metastable phase. Such a synthesis approach oilers a potential route for diversifying intercalation compounds with different stage structures. The first observations of superconductivity in AgxTaS2 were demonstrated in this study. The onset of superconductivity of AgxTaS2 was estimated to be 0.4 and 1.7 K in the samples with x = 0.58 and x = 0.21, respectively. Some anomalies, which were speculatively attributed to charge density wave order, were confirmed in the resistivity measurements of AgxTaS2. The results suggested that the anomalies were closely correlated with the superconducting transition temperature. (C) 2018 The Ceramic Society of Japan. All rights reserved.

Repressive H3K27me3 and active H3K4me2/3 together form bivalent chromatin domains, molecular hallmarks of developmental potential. In the male germline, these domains are thought to persist into sperm to establish totipotency in the next generation. However, it remains unknown how H3K27me3 is established on specific targets in the male germline. Here, we demonstrate that a germline-specific Polycomb protein, SCML2, binds to H3K4me2/3-rich hypomethylated promoters in undifferentiated spermatogonia to facilitate H3K27me3. Thus, SCML2 establishes bivalent domains in the male germline of mice. SCML2 regulates two major classes of bivalent domains: Class I domains are established on developmental regulator genes that are silent throughout spermatogenesis, while class II domains are established on somatic genes silenced during late spermatogenesis. We propose that SCML2-dependent H3K27me3 in the male germline prepares the expression of developmental regulator and somatic genes in embryonic development.

Background: Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl-3H(N)]-3'-fluoro-3'-deoxythythymidine ([3H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498). The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [18F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [18F]FLT. Results: The dynamic pattern of [18F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [18F]FLT phosphorylation (k3) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [18F]FLT forward transport (K1) to reverse transport (k2), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group). Conclusions: Our dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic modeling could provide

Background: A brain single-photon emission computed tomography (SPECT) system using cadmium telluride (CdTe) solid-state detectors was previously developed. This CdTe-SPECT system is suitable for simultaneous dual-radionuclide imaging due to its fine energy resolution (6.6 %). However, the problems of down-scatter and low-energy tail due to the spectral characteristics of a pixelated solid-state detector should be addressed. The objective of this work was to develop a system for simultaneous Tc-99m and I-123 brain studies and evaluate its accuracy. Methods: A scatter correction method using five energy windows (FiveEWs) was developed. The windows are Tc-lower, Tc-main, shared sub-window of Tc-upper and I-lower, I-main, and I-upper. This FiveEW method uses pre-measured responses for primary gamma rays from each radionuclide to compensate for the overestimation of scatter by the triple-energy window method that is used. Two phantom experiments and a healthy volunteer experiment were conducted using the CdTe-SPECT system. A cylindrical phantom and a six-compartment phantom with five different mixtures of Tc-99m and I-123 and a cold one were scanned. The quantitative accuracy was evaluated using 18 regions of interest for each phantom. In the volunteer study, five healthy volunteers were injected with Tc-99m human serum albumin diethylene triamine pentaacetic acid (HSA-D) and scanned (single acquisition). They were then injected with I-123 N-isopropyl-4-iodoamphetamine hydrochloride (IMP) and scanned again (dual acquisition). The counts of the Tc-99m images for the single and dual acquisitions were compared. Results: In the cylindrical phantom experiments, the percentage difference (PD) between the single and dual acquisitions was 5.7 +/- 4.0 % (mean +/- standard deviation). In the six-compartment phantom experiment, the PDs between measured and injected activity for Tc-99m and I-123 were 14.4 +/- 11.0 and 2.3 +/- 1.8 %, respectively. In the volunteer study, the PD betw

Focusing on whole-body uniformity in small-animal single-photon emission computed tomography (SPECT), we examined the optimal helical acquisition parameters using five-pinhole collimators for mouse imaging. SPECT images of an 80-mm-long cylindrical phantom with 99mTc solution were acquired using an Inveon multimodality imaging platform. The bed travels used in this study were 0, 30, 60, 90 and 120 mm, and the numbers of revolutions traversed during the SPECT scan were 1.0, 2.0, 3.0, 4.0, 5.0 and 7.0, respectively. Artifacts that degrade uniformity in reconstructed images were conspicuous when the bed travel was smaller than the object length. Regarding the distal-to-center ratio (DCR) of SPECT values in the object's axial direction, the DCR nearest to the ideal ratio of 1.00 was 1.02 in the optimal uniformity with 4.0 revolutions and a bed travel of 120 mm. Moreover, the helical acquisition using these parameters suppressed the formation of artifacts. We proposed the optimal parameters in whole-body helical SPECT; the bed travel was sufficiently larger than the object length; the 4.0 or more revolutions were required for a pitch of approximately 30 mm/revolution. The optimal acquisition parameters in SPECT to preserve uniformity would contribute to the accurate quantification of whole-body biodistribution. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background: Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl-3H(N)]-3'-fluoro-3'-deoxythythymidine ([3H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498). The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [18F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [18F]FLT. Results: The dynamic pattern of [18F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [18F]FLT phosphorylation (k3) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [18F]FLT forward transport (K1) to reverse transport (k2), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group). Conclusions: Our dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic modeling could provide

Background: Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl-3H(N)]-3'-fluoro-3'-deoxythythymidine ([3H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498). The A498 xenograft was established in nude mice, and the mice were assigned to the control (n = 5) and treatment (n = 5) groups. The mice in the treatment group were orally given sorafenib (20 mg/kg/day p.o.) once daily for 3 days. Twenty-four hours after the treatment, dynamic [18F]FLT PET was performed by small-animal PET. Three-dimensional regions of interest (ROIs) were manually defined for the tumors. A three-compartment model fitting was carried out to estimate four rate constants using the time activity curve (TAC) in the tumor and the blood clearance rate of [18F]FLT. Results: The dynamic pattern of [18F]FLT levels in the tumor significantly changed after the treatment. The rate constant of [18F]FLT phosphorylation (k3) was significantly higher in the treatment group (0.111 ± 0.027 [1/min]) than in the control group (0.082 ± 0.009 [1/min]). No significant changes were observed in the distribution volume, the ratio of [18F]FLT forward transport (K1) to reverse transport (k2), between the two groups (0.556 ± 0.073 and 0.641 ± 0.052 [mL/g] in the control group). Conclusions: Our dynamic PET studies indicated that the increase in FLT level may be caused by the phosphorylation of FLT in the tumor after the sorafenib treatment in the mice bearing a RCC xenograft. Dynamic PET studies with kinetic modeling could provide

Background: A brain single-photon emission computed tomography (SPECT) system using cadmium telluride (CdTe) solid-state detectors was previously developed. This CdTe-SPECT system is suitable for simultaneous dual-radionuclide imaging due to its fine energy resolution (6.6 %). However, the problems of down-scatter and low-energy tail due to the spectral characteristics of a pixelated solid-state detector should be addressed. The objective of this work was to develop a system for simultaneous Tc-99m and I-123 brain studies and evaluate its accuracy. Methods: A scatter correction method using five energy windows (FiveEWs) was developed. The windows are Tc-lower, Tc-main, shared sub-window of Tc-upper and I-lower, I-main, and I-upper. This FiveEW method uses pre-measured responses for primary gamma rays from each radionuclide to compensate for the overestimation of scatter by the triple-energy window method that is used. Two phantom experiments and a healthy volunteer experiment were conducted using the CdTe-SPECT system. A cylindrical phantom and a six-compartment phantom with five different mixtures of Tc-99m and I-123 and a cold one were scanned. The quantitative accuracy was evaluated using 18 regions of interest for each phantom. In the volunteer study, five healthy volunteers were injected with Tc-99m human serum albumin diethylene triamine pentaacetic acid (HSA-D) and scanned (single acquisition). They were then injected with I-123 N-isopropyl-4-iodoamphetamine hydrochloride (IMP) and scanned again (dual acquisition). The counts of the Tc-99m images for the single and dual acquisitions were compared. Results: In the cylindrical phantom experiments, the percentage difference (PD) between the single and dual acquisitions was 5.7 +/- 4.0 % (mean +/- standard deviation). In the six-compartment phantom experiment, the PDs between measured and injected activity for Tc-99m and I-123 were 14.4 +/- 11.0 and 2.3 +/- 1.8 %, respectively. In the volunteer study, the PD betw

PET using semiconductor detectors provides high-quality images of the human brain because of its high spatial resolution. To quantitatively evaluate the delineation of image details in clinical PET images, we used normalized mutual information (NMI) to quantify the similarity with images obtained through MRI. NMI is used to evaluate image quality by determining similarity with a reference image. The aim of this study was to evaluate quantitatively the delineation of image details provided by semiconductor PET.

PET using semiconductor detectors provides high-quality images of the human brain because of its high spatial resolution. To quantitatively evaluate the delineation of image details in clinical PET images, we used normalized mutual information (NMI) to quantify the similarity with images obtained through MRI. NMI is used to evaluate image quality by determining similarity with a reference image. The aim of this study was to evaluate quantitatively the delineation of image details provided by semiconductor PET.

A new design of collimator is proposed that has variable sensitivity and spatial resolution, eliminating the need for exchanging collimators in a gamma camera. Using Monte Carlo simulations, the present article evaluates the shielding of undesirable gamma rays in a parallel-hole collimator. It consists of a number of layers of rectangular holes. These layers consist of alternately stacked fixed and movable collimators. In high-resolution mode, the movable collimators are shifted by half the aperture pitch along the diagonal direction. The first collimator (type A) has 50 layers with fixed thicknesses of 1.2 mm. The second collimator (type B) has 25 layers with a thickness of 1.0 mm on the object side and 25 layers with a thickness of 1.4 mm on the opposite side. The third collimator (type C) has 20 layers with non-uniform thicknesses. The ratios of the maximum artificial peak to the main-peak are calculated for point-source responses. The ratios for types A, B, and C collimators are 0.78, 0.08, and 0.03, respectively. The same performance for shielding undesirable gamma rays is achieved in the type C collimator as for a conventional collimator.

PET using semiconductor detectors provides high-quality images of the human brain because of its high spatial resolution. To quantitatively evaluate the delineation of image details in clinical PET images, we used normalized mutual information (NMI) to quantify the similarity with images obtained through MRI. NMI is used to evaluate image quality by determining similarity with a reference image. The aim of this study was to evaluate quantitatively the delineation of image details provided by semiconductor PET.

Purpose: We analyzed the performance of the Inveon for an integrated small-animal PET/SPECT/CT system and compared the imaging capabilities of the SPECT and the PET components. Methods: For SPECT, energy resolution, tomographic spatial resolution, and system sensitivity were evaluated with 99mTc solution using a single pinhole collimator. For PET, spatial resolution, absolute sensitivity, scatter fraction, and peak noise equivalent count (NEC) were evaluated. A micro-Derenzo phantom, cylindrical phantom, and National Electrical Manufacturers Association NU-4 image quality phantom were scanned to compare SPECT and PET image capabilities, and SPECT and PET bone imaging were performed on a normal rat in vivo. Results: SPECT spatial resolution was 0.84 mm full width at half maximum (FWHM) at a radius of rotation of 25 mm using the 0.5-mm pinhole aperture collimator, while PET spatial resolution was 1.63 mm FWHM at the center. SPECT system sensitivity at a radius of rotation of 25 mm was 35.3 cps/MBq (4 × 10^[-3]%) using 0.5-mm pinhole aperture, while PET absolute sensitivity was 3.2% for 350-650 keV and 3.432 ns. Accordingly, the volume sensitivity of PET was three orders of magnitude higher than that of SPECT. Conclusions: This integrated PET/SPECT/CT system provided high system performance with excellent spatial resolution for SPECT and sensitivity for PET. Based on tracer availability and system performance, SPECT and PET have complementary roles for multi-modality small-animal imaging.

Purpose: We analyzed the performance of the Inveon for an integrated small-animal PET/SPECT/CT system and compared the imaging capabilities of the SPECT and the PET components. Methods: For SPECT, energy resolution, tomographic spatial resolution, and system sensitivity were evaluated with 99mTc solution using a single pinhole collimator. For PET, spatial resolution, absolute sensitivity, scatter fraction, and peak noise equivalent count (NEC) were evaluated. A micro-Derenzo phantom, cylindrical phantom, and National Electrical Manufacturers Association NU-4 image quality phantom were scanned to compare SPECT and PET image capabilities, and SPECT and PET bone imaging were performed on a normal rat in vivo. Results: SPECT spatial resolution was 0.84 mm full width at half maximum (FWHM) at a radius of rotation of 25 mm using the 0.5-mm pinhole aperture collimator, while PET spatial resolution was 1.63 mm FWHM at the center. SPECT system sensitivity at a radius of rotation of 25 mm was 35.3 cps/MBq (4 × 10^[-3]%) using 0.5-mm pinhole aperture, while PET absolute sensitivity was 3.2% for 350-650 keV and 3.432 ns. Accordingly, the volume sensitivity of PET was three orders of magnitude higher than that of SPECT. Conclusions: This integrated PET/SPECT/CT system provided high system performance with excellent spatial resolution for SPECT and sensitivity for PET. Based on tracer availability and system performance, SPECT and PET have complementary roles for multi-modality small-animal imaging.

Purpose: We analyzed the performance of the Inveon for an integrated small-animal PET/SPECT/CT system and compared the imaging capabilities of the SPECT and the PET components. Methods: For SPECT, energy resolution, tomographic spatial resolution, and system sensitivity were evaluated with 99mTc solution using a single pinhole collimator. For PET, spatial resolution, absolute sensitivity, scatter fraction, and peak noise equivalent count (NEC) were evaluated. A micro-Derenzo phantom, cylindrical phantom, and National Electrical Manufacturers Association NU-4 image quality phantom were scanned to compare SPECT and PET image capabilities, and SPECT and PET bone imaging were performed on a normal rat in vivo. Results: SPECT spatial resolution was 0.84 mm full width at half maximum (FWHM) at a radius of rotation of 25 mm using the 0.5-mm pinhole aperture collimator, while PET spatial resolution was 1.63 mm FWHM at the center. SPECT system sensitivity at a radius of rotation of 25 mm was 35.3 cps/MBq (4 × 10^[-3]%) using 0.5-mm pinhole aperture, while PET absolute sensitivity was 3.2% for 350-650 keV and 3.432 ns. Accordingly, the volume sensitivity of PET was three orders of magnitude higher than that of SPECT. Conclusions: This integrated PET/SPECT/CT system provided high system performance with excellent spatial resolution for SPECT and sensitivity for PET. Based on tracer availability and system performance, SPECT and PET have complementary roles for multi-modality small-animal imaging.

Objective: Cerebral blood flow (CBF) estimation with C15O2 PET usually assumes a single tissue compartment model and a fixed brain-blood partition coefficient of water. However, the partition coefficient may change in pathological conditions. The purpose of this study was to investigate the changes of partition coefficient of water in pathological regions and its effect on regional CBF assessment. Methods: Study protocol included 22 patients with occlusive cerebrovascular disease to compare partition coefficients among 3 regions (infarction, non-infarct hypoperfusion, and contralateral) in the pathologic brain (analysis A), and to compare CBF estimated using fixed partition coefficient (CBF fixed) and CBF estimated using floating partition coefficients (CBF float)(analysis B). Results: Partition coefficient in the infarction (0.55 ± 0.07 ml/g) was lower than that in contralateral normal cortex (0.68 ± 0.05 ml/g), whereas non-infarct hypoperfusion did not show a significant change (0.67 ± 0.06 ml/g). As a result, use of a fixed partition coefficient of normal volunteers (0.70 ml/g) resulted in an underestimation in rCBF by 12% in infarction area (P<0.05), while estimation errors were smaller and induced no significant difference in non-infarct hypoperfusion area or in contralateral areas. Conclusions: Partition coefficient is stable except for the infarction, and CBF estimation using a fixed partition coefficient of normal volunteers provides clinically appreciable information in patients with cerebrovascular disease.

Objective: Cerebral blood flow (CBF) estimation with C15O2 PET usually assumes a single tissue compartment model and a fixed brain-blood partition coefficient of water. However, the partition coefficient may change in pathological conditions. The purpose of this study was to investigate the changes of partition coefficient of water in pathological regions and its effect on regional CBF assessment. Methods: Study protocol included 22 patients with occlusive cerebrovascular disease to compare partition coefficients among 3 regions (infarction, non-infarct hypoperfusion, and contralateral) in the pathologic brain (analysis A), and to compare CBF estimated using fixed partition coefficient (CBF fixed) and CBF estimated using floating partition coefficients (CBF float)(analysis B). Results: Partition coefficient in the infarction (0.55 ± 0.07 ml/g) was lower than that in contralateral normal cortex (0.68 ± 0.05 ml/g), whereas non-infarct hypoperfusion did not show a significant change (0.67 ± 0.06 ml/g). As a result, use of a fixed partition coefficient of normal volunteers (0.70 ml/g) resulted in an underestimation in rCBF by 12% in infarction area (P<0.05), while estimation errors were smaller and induced no significant difference in non-infarct hypoperfusion area or in contralateral areas. Conclusions: Partition coefficient is stable except for the infarction, and CBF estimation using a fixed partition coefficient of normal volunteers provides clinically appreciable information in patients with cerebrovascular disease.

Purpose: We analyzed the performance of the Inveon for an integrated small-animal PET/SPECT/CT system and compared the imaging capabilities of the SPECT and the PET components. Methods: For SPECT, energy resolution, tomographic spatial resolution, and system sensitivity were evaluated with 99mTc solution using a single pinhole collimator. For PET, spatial resolution, absolute sensitivity, scatter fraction, and peak noise equivalent count (NEC) were evaluated. A micro-Derenzo phantom, cylindrical phantom, and National Electrical Manufacturers Association NU-4 image quality phantom were scanned to compare SPECT and PET image capabilities, and SPECT and PET bone imaging were performed on a normal rat in vivo. Results: SPECT spatial resolution was 0.84 mm full width at half maximum (FWHM) at a radius of rotation of 25 mm using the 0.5-mm pinhole aperture collimator, while PET spatial resolution was 1.63 mm FWHM at the center. SPECT system sensitivity at a radius of rotation of 25 mm was 35.3 cps/MBq (4 × 10^[-3]%) using 0.5-mm pinhole aperture, while PET absolute sensitivity was 3.2% for 350-650 keV and 3.432 ns. Accordingly, the volume sensitivity of PET was three orders of magnitude higher than that of SPECT. Conclusions: This integrated PET/SPECT/CT system provided high system performance with excellent spatial resolution for SPECT and sensitivity for PET. Based on tracer availability and system performance, SPECT and PET have complementary roles for multi-modality small-animal imaging.

An autoradiography method revealed intratumoral inhomogeneity in various solid tumors. It is becoming increasingly important to estimate intratumoral inhomogeneity. However, with low spatial resolution and high scatter noise, it is difficult to detect intratumoral inhomogeneity in clinical settings. We developed a new PET system with CdTe semiconductor detectors to provide images with high spatial resolution and low scatter noise. Both phantom images and patients’ images were analyzed to evaluate intratumoral inhomogeneity. Methods: This study was performed with a cold spot phantom that had 6-mm-diameter cold sphenoid defects, a dual-cylinder phantom with an adjusted concentration of 1:2, and an ''H''-shaped hot phantom. These were surrounded with water. Phantom images and 18F-FDG PET images of patients with nasopharyngeal cancer were compared with conventional bismuth germanate PET images. Profile curves for the phantoms were measured as peak-to-valley ratios to define contrast. Intratumoral inhomogeneity and tumor edge sharpness were evaluated on the images of the patients. Results: The contrast obtained with the semiconductor PET scanner (1.53) was 28% higher than that obtained with the conventional scanner (1.20) for the 6-mm-diameter cold sphenoid phantom. The contrast obtained with the semiconductor PET scanner (1.43) was 27% higher than that obtained with the conventional scanner (1.13) for the dual-cylinder phantom. Similarly, the 2-mm cold region between 1-mm hot rods was identified only by the new PET scanner and not by the conventional scanner. The new PET scanner identified intratumoral inhomogeneity in more detail than the conventional scanner in 6 of 10 patients. The tumor edge was sharper on the images obtained with the new PET scanner than on those obtained with the conventional scanner. Conclusion: These phantom and clinical studies suggested that this new PET scanner has the potential for better identification of intratumoral inhomogeneity, probabl

An autoradiography method revealed intratumoral inhomogeneity in various solid tumors. It is becoming increasingly important to estimate intratumoral inhomogeneity. However, with low spatial resolution and high scatter noise, it is difficult to detect intratumoral inhomogeneity in clinical settings. We developed a new PET system with CdTe semiconductor detectors to provide images with high spatial resolution and low scatter noise. Both phantom images and patients’ images were analyzed to evaluate intratumoral inhomogeneity. Methods: This study was performed with a cold spot phantom that had 6-mm-diameter cold sphenoid defects, a dual-cylinder phantom with an adjusted concentration of 1:2, and an ''H''-shaped hot phantom. These were surrounded with water. Phantom images and 18F-FDG PET images of patients with nasopharyngeal cancer were compared with conventional bismuth germanate PET images. Profile curves for the phantoms were measured as peak-to-valley ratios to define contrast. Intratumoral inhomogeneity and tumor edge sharpness were evaluated on the images of the patients. Results: The contrast obtained with the semiconductor PET scanner (1.53) was 28% higher than that obtained with the conventional scanner (1.20) for the 6-mm-diameter cold sphenoid phantom. The contrast obtained with the semiconductor PET scanner (1.43) was 27% higher than that obtained with the conventional scanner (1.13) for the dual-cylinder phantom. Similarly, the 2-mm cold region between 1-mm hot rods was identified only by the new PET scanner and not by the conventional scanner. The new PET scanner identified intratumoral inhomogeneity in more detail than the conventional scanner in 6 of 10 patients. The tumor edge was sharper on the images obtained with the new PET scanner than on those obtained with the conventional scanner. Conclusion: These phantom and clinical studies suggested that this new PET scanner has the potential for better identification of intratumoral inhomogeneity, probabl

Objectives: Small animal imaging has recently been focused on basic nuclear medicine. We have designed and built a small animal SPECT imaging system using a semiconductor camera and a newly designed collimator. We assess the performance of this system for small object imaging. Methods: We employed an MGC1500 (Acrorad Co.) camera including a CdTe semiconductor. The pixel size was 1.4 mm/pixel. We designed and produced a parallel-hole collimator with 20-mm hole length. Our SPECT system consisted of a semiconductor camera with the subject holder set on an electric rotating stage controlled by a computer. We compared this system with a conventional small animal SPECT system comprising a SPECT-2000H scanner with four Anger type cameras and pinhole collimators. The count rate linearity for estimation of the scatter was evaluated for a piechart phantom containing different concentrations of 99mTc. We measured the FWHM of the 99mTc SPECT line source along with scatter. The system volume sensitivity was examined using a flood source phantom which was 35 mm long with a 32-mm inside diameter. Additionally, an in vivo myocardial perfusion SPECT study was performed with a rat. Results: With regards to energy resolution, the semiconductor camera (5.6%) was superior to the conventional Anger type camera (9.8%). In the count rate linearity evaluation, the regression lines of the SPECT values were y = 0.019x + 0.031 (r2 = 0.999) for our system and y = 0.018x + 0.060 (r2 = 0.997) for the conventional system. Thus, the scatter count using the semiconductor camera was less than that using the conventional camera. FWHMs of our system and the conventional system were 2.9 ± 0.1 and 2.0 ± 0.1 mm, respectively. Moreover, the system volume sensitivity of our system [0.51 kcps/(MBq/ ml)/cm] was superior to that of the conventional system [0.44 kcps/(MBq/ml)/cm]. Our system provided clear images of the rat myocardium, sufficient for practical use in small animal imaging. Conclusions: Our SPECT

We have developed a pinhole collimator for small animal imaging using dual-isotopes, such as gamma and positron emitters. A lead cylinder containing a pinhole was placed around the subject (a small animal). The cylinder was equipped with a non-collimator gamma camera, and dual-isotope (99mTc-MIBI and 18F-FDG) SPECT was performed on a Wistar King Aptekman/hok (WKAH) rat. System planar sensitivity and Full-Width at Half-Maximum (FWHM) were measured for each radionuclide. System planar sensitivities for 99mTc and 18F SPECT were 2 and 7 cps/MBq, respectively. FWHMs for 99mTc and 18F SPECT were 2.0±0.5 and 2.7±0.5 mm, respectively. The collimator is relatively light (23 kg), and thus SPECT projection data could be acquired by rotating the gamma camera while the object remained stationary. The pinhole collimator can be used with a conventional rotating gamma camera. The present study demonstrated that it is possible to image organs in vivo in sufficient detail using the newly developed pinhole collimator. Further refinements to the experimental procedure may provide simultaneous high-resolution imaging of small animals using positron and gamma emitters with this collimator.

We have developed a pinhole collimator for small animal imaging using dual-isotopes, such as gamma and positron emitters. A lead cylinder containing a pinhole was placed around the subject (a small animal). The cylinder was equipped with a non-collimator gamma camera, and dual-isotope (99mTc-MIBI and 18F-FDG) SPECT was performed on a Wistar King Aptekman/hok (WKAH) rat. System planar sensitivity and Full-Width at Half-Maximum (FWHM) were measured for each radionuclide. System planar sensitivities for 99mTc and 18F SPECT were 2 and 7 cps/MBq, respectively. FWHMs for 99mTc and 18F SPECT were 2.0±0.5 and 2.7±0.5 mm, respectively. The collimator is relatively light (23 kg), and thus SPECT projection data could be acquired by rotating the gamma camera while the object remained stationary. The pinhole collimator can be used with a conventional rotating gamma camera. The present study demonstrated that it is possible to image organs in vivo in sufficient detail using the newly developed pinhole collimator. Further refinements to the experimental procedure may provide simultaneous high-resolution imaging of small animals using positron and gamma emitters with this collimator.

Gated myocardial perfusion single-photon emission tomography (SPET) has been used for the measurement of left ventricular (LV) function and validated by means of comparison with other imaging modalities. We have designed a new dynamic myocardial phantom in order to validate the LV function as assessed by the use of gated myocardial perfusion SPET. The phantom consists of two half-ellipsoids (an endocardial surface and an epicardial surface) and a thorax. The myocardial space is filled with a radioactive solution. The endocardial surface moves continuously towards and away from the epicardial surface in the longitudinal axis to vary the LV volume [143 ml at end-diastole (ED), 107 ml at end-systole (ES)] and thickness (apex 8 mm at ED and 26 mm at ES, midplane 8 mm). The mean values of wall motion (WM) for the apical midplane region and the basal midplane region were 5 mm and 2 mm, respectively. Gated myocardial SPET was performed during 8 and 16 intervals. These projection data sets were processed using a Butterworth filter with an order of 5 and a critical frequency of 0.34 cycles/cm. LV function was calculated using the quantitative gated SPET (QGS) algorithm. The LV function values estimated by gated SPET during 16 intervals [22% for ejection fraction (EF), 3.7 mm for WM of the apical midplane, 1.7 mm for WM of the basal midplane] closely resembled actual LV functions [25% for EF, 5 mm for WM of the apical midplane, 2 mm for WM of the basal midplane]. However, the estimated values during 8 intervals were smaller than those during 16 intervals (19% for EF, 3.3 mm for WM of the apical-midplane, 1.1 mm for WM of the basal-midplane). The estimated LV volumes closely correlated with the actual volumes (r=0.99 for 16 intervals, r=0.95 for 8 intervals). Utilizing this phantom, LV function estimated using gated myocardial SPET can be compared with actual values.

Gated myocardial perfusion single-photon emission tomography (SPET) has been used for the measurement of left ventricular (LV) function and validated by means of comparison with other imaging modalities. We have designed a new dynamic myocardial phantom in order to validate the LV function as assessed by the use of gated myocardial perfusion SPET. The phantom consists of two half-ellipsoids (an endocardial surface and an epicardial surface) and a thorax. The myocardial space is filled with a radioactive solution. The endocardial surface moves continuously towards and away from the epicardial surface in the longitudinal axis to vary the LV volume [143 ml at end-diastole (ED), 107 ml at end-systole (ES)] and thickness (apex 8 mm at ED and 26 mm at ES, midplane 8 mm). The mean values of wall motion (WM) for the apical midplane region and the basal midplane region were 5 mm and 2 mm, respectively. Gated myocardial SPET was performed during 8 and 16 intervals. These projection data sets were processed using a Butterworth filter with an order of 5 and a critical frequency of 0.34 cycles/cm. LV function was calculated using the quantitative gated SPET (QGS) algorithm. The LV function values estimated by gated SPET during 16 intervals [22% for ejection fraction (EF), 3.7 mm for WM of the apical midplane, 1.7 mm for WM of the basal midplane] closely resembled actual LV functions [25% for EF, 5 mm for WM of the apical midplane, 2 mm for WM of the basal midplane]. However, the estimated values during 8 intervals were smaller than those during 16 intervals (19% for EF, 3.3 mm for WM of the apical-midplane, 1.1 mm for WM of the basal-midplane). The estimated LV volumes closely correlated with the actual volumes (r=0.99 for 16 intervals, r=0.95 for 8 intervals). Utilizing this phantom, LV function estimated using gated myocardial SPET can be compared with actual values.