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Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [ 11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [ 11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Artificial intelligence (AI) has been applied to various medical imaging tasks, such as computer-aided diagnosis. Specifically, deep learning techniques such as convolutional neural network (CNN) and generative adversarial network (GAN) have been extensively used for medical image generation. Image generation with deep learning has been investigated in studies using positron emission tomography (PET). This article reviews studies that applied deep learning techniques for image generation on PET. We categorized the studies for PET image generation with deep learning into three themes as follows: (1) recovering full PET data from noisy data by denoising with deep learning, (2) PET image reconstruction and attenuation correction with deep learning and (3) PET image translation and synthesis with deep learning. We introduce recent studies based on these three categories. Finally, we mention the limitations of applying deep learning techniques to PET image generation and future prospects for PET image generation., (© 2021. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Visualizing the dynamics of cesium (Cs) is desirable to understand the impact of radiocesium when accidentally ingested or inhaled by humans. However, visualization of radiocesium in vivo is currently limited to plants. Herein, we describe a method for the production and purification of 127 Cs and its use in visualizing Cs dynamics in a living animal. The positron-emitting nuclide 127 Cs was produced using the 127 I (α, 4n) 127 Cs reaction, which was induced by irradiation of sodium iodide with a 4 He 2+ beam from a cyclotron. We excluded sodium ions by using a material that specifically adsorbs Cs as a purification column and successfully eluted 127 Cs by flowing a solution of ammonium sulfate into the column. We injected the purified 127 Cs tracer solution into living rats and the dynamics of Cs were visualized using positron emission tomography; the distributional images showed the same tendency as the results of previous studies using disruptive methods. Thus, this method is useful for the non-invasive investigation of radiocesium in a living animal.

The D-shuttle dosimeter technique is a convenient approach for estimating the radiation dosimetry in a positron emission tomography (PET) study that employs multiple D-shuttle dosimeters attached to the body surface of a patient. To bring this technique into clinical usage, it is very important to evaluate its performance by investigating the bias associated with D-shuttle dosimeter positioning and by comparing the estimates with those of the whole-body dynamic PET imaging technique. The torso cavity and six spheres of the NEMA body phantom were filled with 18 F-FDG solution, and then, the phantom was imaged for 1 h. We assumed the mislocated positioning of the D-shuttle dosimeters by shifting them in the z-direction (upper) in a range of 1-5 cm from the original positions. The cumulative radioactivities, absorbed doses, and effective dose were estimated using accurate and mislocated positions of the D-shuttle dosimeters. For comparison, the cumulative radioactivities were also estimated from the PET images, and then, the absorbed doses and effective dose were computed. The maximum bias of the average estimated cumulated radioactivities and the effective doses was - 15.0% and - 19.7% for the 1 cm shifted positions, respectively. The ratios of absorbed doses obtained from D-shuttle and PET measurement against the actual values were between 0.9 and 1.3, and 0.7 and 1.0, respectively. The bias associated with the D-shuttle dosimeter positions was significant and probably consistent, and both dosimetric techniques exhibited good performance in this phantom study.

Background: Multi-modal brain image registration is a prerequisite for accurate mapping of brain structure and function in neuroscience. Image registration is commonly performed using automated software; however, its accuracy decreases when images differ in modality, contrast, uniformity, and resolution. This limitation could be overcome by using an external reference point; however, high-contrast agents in multi-modal imaging have not been previously reported., New Methods: Here, we propose a novel multi-modal fiducial marker that contains Tungsten solution and provides high contrast in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET). The basic characteristics of this multi-modal marker were investigated by assessing major sources of image contrast in the following modalities: density and T1-, T2-relaxivity in comparison with conventional contrast agents., Results: Tungsten solution had lower T1- and T2-relaxivity and high solubility, and showed high contrast in T1- and T2-weighted MR and CT images at a high-density concentration (˜3.0 g/mL), whereas other conventional solutions did not show sufficient contrast in either CT or MRI., Comparison With Existing Methods: The use of this Tungsten-based multi-modal marker allowed more accurate registration than a software-only method in phantom and animal experiments. Application of this method demonstrated accurate cortical surface mapping of neurotransmitter function (dopamine transporter, DAT) using PET and MRI, and provided a neurobiologically relevant cortical distribution consistent with previous literature on histology-based DAT immunoreactivity., Conclusions: The Tungsten-based multi-modal fiducial marker is non-radioactive, easy to handle, and aids precise registration across different modalities of brain imaging., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Purposes: Subject's motion during brain PET scan degrades spatial resolution and quantification of PET images. To suppress these effects, rigid-body motion correction systems have been installed in commercial PET scanners. In this study, we systematically compare the accuracy of motion correction among 3 commercial PET scanners using a reproducible experimental acquisition protocol., Methods: A cylindrical phantom with two 22 Na point sources was placed on a customized base to enable two types of motion, 5° yaw and 15° pitch rotations. Repetitive PET scans (5 min × 5 times) were performed at rest and under 2 motion conditions using 3 clinical PET scanners: the Eminence STARGATE G/L PET/CT (STARGATE) (Shimadzu Corp.), the SET-3000 B/X PET (SET-3000) (Shimadzu Corp.), and the Biograph mMR PET/MR (mMR) (Siemens Healthcare) systems. For STARGATE and SET-3000, the Polaris Vicra (Northern Digital Inc.) optical tracking system was used for frame-by-frame motion correction. For Biograph mMR, sequential MR images were simultaneously acquired with PET and used for LOR-based motion correction. All PET images were reconstructed by FBP algorithm with 1 × 1 mm pixel size. To evaluate the accuracy of motion correction, FWHMs and spherical ROI values were analyzed., Results: The percent differences (%diff) in averaged FWHMs of point sources at 4 cm off-center between motion-corrected and static images were 0.77 ± 0.16 (STARGATE), 2.4 ± 0.34 (SET-3000), and 11 ± 1.0% (mMR) for a 5° yaw and 2.3 ± 0.37 (STARGATE) and 1.1 ± 0.60 (SET-3000) for a 15° pitch respectively. The averaged %diff between ROI values of motion-corrected images and static images were less than 2.0% for all conditions., Conclusions: In this study, we proposed a reproducible experimental framework to allow the systematic validation and comparison of multiple motion tracking and correction methodologies among different PET/CT and PET/MR commercial systems. Our proposed validation platform may be useful for future studies evaluating state-of-the-art motion correction strategies in clinical PET imaging.

With the increasing incidence of dementia worldwide, the frequent use of amyloid and tau positron emission tomography imaging requires low-dose protocols for the differential diagnoses of various neurodegenerative diseases and the monitoring of disease progression. In this study, we investigated the feasibility to reduce the PET dose without a significant loss of quantitative accuracy in 3D dynamic row action maximum likelihood algorithm-reconstructed PET images using [ 11 C]PIB and [ 18 F]THK5351. Eighteen cognitively normal young controls, cognitively normal elderly controls, and patients with probable Alzheimer's disease (n = 6 each), were included. Reduced doses were simulated by randomly sampling half and quarter of the full counts in list mode data for one independent realization at each simulated dose. Bias was evaluated between the reduced dose from the full dose of standardized uptake value ratio (SUVR), distribution volume ratio (DVR) from reference Logan, and non-displaceable binding potential (BP ND ) from simplified reference tissue model (SRTM). DVR yielded the least bias at low dose compared to SUVR and BP ND , and thus, is highly recommended. The dose of [ 18 F]THK5351 and [ 11 C]PIB can be reduced to a quarter of the full dose using DVR for evaluation, whereas the dose can only be reduced to half and a quarter of the full dose for [ 18 F]THK5351 and [ 11 C]PIB using SUVR. BP ND showed inconsistent trend and large bias at low dose. The feasibility of dose reduction was dependent on the selected parameters of interest, reconstruction algorithms, reference regions, and to a lesser degree by motion effects.

Purpose: Internal radiation dosimetry plays an important role in ensuring the safe use of positron emission tomography (PET) technology and is a legal requirement in most countries. We propose a new technique to estimate the internal radiation dose in PET studies by means of multiple D-shuttle dosimeters attached on the body surface of the patient., Methods: Radioactivity in a source organ was estimated iteratively using measurements from multiple D-shuttle dosimeters with a maximum-likelihood expectation-maximization (MLEM) algorithm with dose response from a source to a D-shuttle dosimeter computed by Monte Carlo simulation. To validate our technique, we performed a phantom study using a National Electrical Manufacturers Association (NEMA) body phantom. The fillable compartments (torso cavity and six spheres) of the phantom were filled with 18 F-FDG mixed with pure water using an 800:1 sphere-to-background radioactivity concentration ratio. The radioactivity concentrations present in the torso cavity and six spheres were 0.00165 MBq/mL and 1.32 MBq/mL, respectively. The initial radioactivities of the torso cavity and six spheres (treated as source organs) were 15.9 MBq (torso cavity), 34.7 MBq (37 mm sphere), 15.1 MBq (28 mm sphere), 7.27 MBq (22 mm sphere), 3.26 MBq (17 mm sphere), 1.54 MBq (13 mm sphere), and 0.697 MBq (10 mm sphere). Eleven D-shuttle dosimeters were attached to the NEMA body phantom surface to obtain information on body surface dose and a mathematical NEMA body phantom has been modeled in the Heavy Ion Transport Code System (PHITS) Monte Carlo simulation code., Results: Radioactivity was estimated in 2 min intervals over a 110-min total dose time using our proposed technique. A significant correlation (R 2 = 0.992) was found between actual radioactivity and estimated radioactivity at every 2 min interval for each source organ. The estimated initial radioactivity (mean with standard deviation) was 16.5 ± 0.311 MBq (torso cavity), 33.0 ± 0.624 MBq (37 mm sphere), 15.7 ± 0.189 MBq (28 mm sphere), 7.11 ± 0.738 MBq (22 mm sphere), 4.17 ± 0.083 MBq (17 mm sphere), 1.48 ± 0.469 MBq (13 mm sphere), and 0.865 ± 0.313 MBq (10 mm sphere), which were very close to the actual initial radioactivity measurements for each source organ., Conclusions: The phantom study showed that our technique worked successfully. This technique could be used to estimate internal radiation dosimetry in a clinical PET study., (© 2018 American Association of Physicists in Medicine.)

Attenuation correction (AC) is required for accurate quantitative evaluation of small animal PET data. Our objective was to compare three AC methods in the small animal Clairvivo-PET scanner. The three AC methods involve applying attenuation coefficient maps generated by simulating a cylindrical map (SAC), segmenting the emission data (ESAC), and segmenting the transmission data (TSAC), imaged using a 137 Cs single-photon source. Investigation was carried out using a 65 mm uniform cylinder and an NEMA NU4 2008 mouse phantom, filled with water or tungsten liquid, to mimic bone. Evaluation was carried out using the difference of the segmented map volume from the known cylindrical phantom volume, the recovery of the radioactivity concentration, and the line profiles. The optimal transmission scan time for achieving accurate AC using TSAC was determined using 5, 10, 15, 20, and 25 min transmission scan time. The effects of scatter correction and reconstruction algorithms on ESAC were investigated. SAC showed the best performance but was unable to correct for different tissues and the scanner bed, and faced difficulty with correct positioning of the attenuation coefficient map. ESAC was affected by scatter correction and reconstruction algorithm, and may result in poor boundary delineation, and hence was unreliable. TSAC showed reasonable performance but required further optimization of the default segmentation setting. A minimum transmission scan time of 20 min is recommended for Clairvivo-PET using 137 Cs source to ensure that sufficient transmission counts are obtained to generate accurate attenuation coefficient map.

Our study aimed to develop a method to mathematically predict the kinetic parameters K 1 (influx rate constant), k 2 (efflux rate constant), and BP ND (nondisplaceable binding potential) of amyloid PET tracers and obtain SUV ratios (SUVRs) from predicted time-activity curves of target and reference regions. Methods: We investigated 10 clinically applied amyloid PET radioligands: 11 C-Pittsburgh compound B, 11 C-BF-227, 11 C-AZD2184, 11 C-SB-13, 18 F-FACT, 18 F-florbetapir, 18 F-florbetaben, 18 F-flutemetamol, 18 F-FDDNP, and 18 F-AZD4694. For each tracer, time-activity curves of both target and reference regions were generated using a simplified 1-tissue-compartment model, with an arterial plasma input function and the predicted kinetic parameters. K 1 , k 2 , and BP ND were derived from the lipophilicity (log P ), apparent volume, free fraction in plasma, free fraction in tissue, dissociation constant, and density of amyloid β using biomathematic modeling. Density was fixed at 3 nM to represent healthy control conditions and 50 nM to represent severe Alzheimer disease (AD). Predicted SUVRs for the healthy and AD groups were then obtained by dividing the integrated time-activity curve of the target region by that of the reference region. To validate the presented method, the predicted K 1 , k 2 , BP ND , and SUVR for the healthy and AD groups were compared with the respective clinically observed values. Results: The correlation between predicted and clinical kinetic parameters had an R 2 value of 0.73 for K 1 in the healthy group, 0.71 for K 1 in the AD group, 0.81 for k 2 in the healthy group, 0.85 for k 2 in the AD group, and 0.63 for BP ND in the AD group. The regression relationship between the predicted SUVR ( y ) and the clinical SUVR ( x ) for the healthy and the AD groups was y = 2.73 x - 2.11 ( R 2 = 0.72). Conclusion: The proposed method showed a good correlation between predicted and clinical SUVR for the 10 clinically applied amyloid tracers., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To suppress partial volume effect (PVE) in brain PET, there have been many algorithms proposed. However, each methodology has different property due to its assumption and algorithms. Our aim of this study was to investigate the difference among partial volume correction (PVC) method for tau and amyloid PET study., Methods: We investigated two of the most commonly used PVC methods, Müller-Gärtner (MG) and geometric transfer matrix (GTM) and also other three methods for clinical tau and amyloid PET imaging. One healthy control (HC) and one Alzheimer's disease (AD) PET studies of both [ 18 F]THK5351 and [ 11 C]PIB were performed using a Eminence STARGATE scanner (Shimadzu Inc., Kyoto, Japan). All PET images were corrected for PVE by MG, GTM, Labbé (LABBE), Regional voxel-based (RBV), and Iterative Yang (IY) methods, with segmented or parcellated anatomical information processed by FreeSurfer, derived from individual MR images. PVC results of 5 algorithms were compared with the uncorrected data., Results: In regions of high uptake of [ 18 F]THK5351 and [ 11 C]PIB, different PVCs demonstrated different SUVRs. The degree of difference between PVE uncorrected and corrected depends on not only PVC algorithm but also type of tracer and subject condition., Conclusion: Presented PVC methods are straight-forward to implement but the corrected images require careful interpretation as different methods result in different levels of recovery.

Introduction: The purpose of this study was to compare two amyloid imaging agents, [(11)C]BF227 and [(18)F]FACT (derivative from [(11)C]BF227) through quantitative pharmacokinetics analysis in human brain., Methods: Positron emission tomography studies were performed on six elderly healthy control (HC) subjects and seven probable Alzheimer's disease (AD) patients with [(11)C]BF227 and 10 HC subjects and 10 probable AD patients with [(18)F]FACT. Data from nine regions of interest were analyzed by several approaches, namely non-linear least-squared fitting methods with arterial input functions (one-tissue compartment model(1TCM), two-tissue compartment model (2TCM)), Logan plot, and linearized methods with reference region (Reference Logan plot (RefLogan), MRTM0, MRTM2). We also evaluated SUV and SUVR for both tracers. The parameters estimated by several approaches were compared between two tracers for detectability of differences between HC and AD patients., Results: For [(11)C]BF227, there were no significant difference of VT (2TCM, 1TCM) and SUV in all regions (Student t-test; p<0.05) and significant differences in the DVRs (Logan, RefLogan, and MRTM2) and SUVRs in six neocortical regions (p<0.05) between the HC and AD groups. For [(18)F]FACT, significant differences in DVRs (RefLogan, MRTM0, and MRTM2) were observed in more than four neocortical regions between the HC and AD groups (p<0.05), and the significant differences were found in SUVRs for two neocortical regions (inferior frontal coretex and lateral temporal coretex). Our results showed that both tracers can clearly distinguish between HC and AD groups although the pharmacokinetics and distribution patterns in brain for two tracers were substantially different., Conclusion: This study revealed that although the PET amyloid imaging agents [(11)C]BF227 and [(18)F]FACT have similar chemical and biological properties, they have different pharmacokinetics, and caution must be paid for usage of the tracers., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11)C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands., Methods: The distribution of (11)C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11)C-DNP (45.0 ± 10.7 MBq). The whole-body distribution of the (11)C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs., Results: The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11)C-DNP in the body (following the liver) (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3), respectively), indicating that the distribution of (11)C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands., Conclusions: We demonstrated the whole-body distribution of (11)C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11)C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

Purpose: Cerenkov-light imaging is a new molecular imaging technology that detects visible photons from high-speed electrons using a high sensitivity optical camera. However, the merit of Cerenkov-light imaging remains unclear. If a PET/Cerenkov-light hybrid imaging system were developed, the merit of Cerenkov-light imaging would be clarified by directly comparing these two imaging modalities., Methods: The authors developed and tested a PET/Cerenkov-light hybrid imaging system that consists of a dual-head PET system, a reflection mirror located above the subject, and a high sensitivity charge coupled device (CCD) camera. The authors installed these systems inside a black box for imaging the Cerenkov-light. The dual-head PET system employed a 1.2×1.2×10 mm3 GSO arranged in a 33 × 33 matrix that was optically coupled to a position sensitive photomultiplier tube to form a GSO block detector. The authors arranged two GSO block detectors 10 cm apart and positioned the subject between them. The Cerenkov-light above the subject is reflected by the mirror and changes its direction to the side of the PET system and is imaged by the high sensitivity CCD camera., Results: The dual-head PET system had a spatial resolution of ∼1.2 mm FWHM and sensitivity of ∼0.31% at the center of the FOV. The Cerenkov-light imaging system's spatial resolution was ∼275 μm for a 22Na point source. Using the combined PET/Cerenkov-light hybrid imaging system, the authors successfully obtained fused images from simultaneously acquired images. The image distributions are sometimes different due to the light transmission and absorption in the body of the subject in the Cerenkov-light images. In simultaneous imaging of rat, the authors found that 18F-FDG accumulation was observed mainly in the Harderian gland on the PET image, while the distribution of Cerenkov-light was observed in the eyes., Conclusions: The authors conclude that their developed PET/Cerenkov-light hybrid imaging system is useful to evaluate the merits and the limitations of Cerenkov-light imaging in molecular imaging research.

Since a high resolution PET system is needed for small animal imaging, especially for mouse studies, we developed a new small animal PET system that decreased the size of the scintillators to less than 1 mm. Our developed PET system used 0.5 × 0.7 × 5 mm(3) LYSO pixels arranged in an 11 × 13 matrix to form a block with a 0.1 mm BaSO4 reflector between the pixels. Two LYSO blocks were optically coupled to two optical fiber based angled image guides. These LYSO blocks and image guides were coupled to a Si-PM array (Hamamatsu MPPC S11064-050P) to form a block detector. Eight block detectors (16 LYSO blocks) were arranged in a 34 mm inner diameter ring to form a small animal PET system. The block detector showed good separation for the 22 × 13 LYSO pixels in the two-dimensional position histogram. The energy resolution was 20% full-with at half-maximum (FWHM) for 511 keV gamma photons. The transaxial resolution reconstructed by filtered backprojection was 0.71 to 0.75 mm FWHM and the axial resolution was 0.70 mm. The point source sensitivity was 0.24% at the central axial field-of-view. High resolution mouse images were obtained using our PET system. The developed ultrahigh resolution PET system showed attractive images for small animal studies and has a potential to provide new findings in molecular imaging researches.

Positron emission tomography (PET) with (15)O tracers provides essential information in patients with cerebral vascular disorders, such as cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO(2)). However, most of techniques require an additional C(15)O scan for compensating cerebral blood volume (CBV). We aimed to establish a technique to calculate all functional images only from a single dynamic PET scan, without losing accuracy or statistical certainties. The technique was an extension of previous dual-tracer autoradiography (DARG) approach, but based on the basis function method (DBFM), thus estimating all functional parametric images from a single session of dynamic scan acquired during the sequential administration of H(2)(15)O and (15)O(2). Validity was tested on six monkeys by comparing global OEF by PET with those by arteriovenous blood sampling, and tested feasibility on young healthy subjects. The mean DBFM-derived global OEF was 0.57±0.06 in monkeys, in an agreement with that by the arteriovenous method (0.54±0.06). Image quality was similar and no significant differences were seen from DARG; 3.57%±6.44% and 3.84%±3.42% for CBF, and -2.79%±11.2% and -6.68%±10.5% for CMRO(2). A simulation study demonstrated similar error propagation between DBFM and DARG. The DBFM method enables accurate assessment of CBF and CMRO(2) without additional CBV scan within significantly shortened examination period, in clinical settings.

Unlabelled: PET with (15)O gas has been used for the quantitative measurement of cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) in humans. However, several technical difficulties limit its use in experiments on small animals. Herein, we describe the application of the (15)O gas steady-state inhalation method for normal anesthetized rats., Methods: Eight normal male Sprague-Dawley rats (mean body weight ± SD, 268 ± 14 g) under anesthesia were investigated by (15)O-labeled gas PET. After tracheotomy, an airway tube was placed in the trachea, and the animals were connected to a ventilator (tidal volume, 3 cm(3); frequency, 60/min). The CBF and OEF were measured according to the original steady-state inhalation technique under artificial ventilation with (15)O-CO(2) and (15)O-O(2) gases delivered through the radioactive gas stabilizer. CBV was measured by (15)O-CO gas inhalation and corrected for the intravascular hemoglobin-bound (15)O-O(2). Arterial blood sampling was performed during each study to measure the radioactivity of the whole blood and plasma. MR image was performed with the same acrylic animal holder immediately after the PET. Regions of interest were placed on the whole brain of the PET images with reference to the semiautomatically coregistered PET/MR fused images., Results: The data acquisition time for the whole PET experiment in each rat was 73.3 ± 5.8 (range, 68-85) min. In both the (15)O-CO(2) and the (15)O-O(2) studies, the radioactivity count of the brain reached a steady state by approximately 10 min after the start of continuous inhalation of the gas. The quantitative PET data of the whole brain were as follows: CBF, 32.3 ± 4.5 mL/100 mL/min; CMRO(2), 3.23 ± 0.42 mL/100 mL/min; OEF, 64.6% ± 9.1%; and CBV, 5.05 ± 0.45 mL/100 mL., Conclusion: Although further technical improvements may be needed, this study demonstrated the feasibility of quantitative PET measurement of CBF, OEF, and CMRO(2) using the original steady-state inhalation method of (15)O-CO(2) and (15)O-O(2) gases and measurement of CBV using the (15)O-CO gas inhalation method in the brain of normal anesthetized rats.

In clinical cardiac positron emission tomography using (15)O-water, significant tracer accumulation is observed not only in the heart but also in the liver and lung, which are partially outside the field-of-view. In this work, we investigated the effects of scatter on quantitative myocardium blood flow (MBF) and perfusable tissue fraction (PTF) by a precise Monte Carlo simulation (Geant4) and a numerical human model. We assigned activities to the heart, liver, and lung of the human model with varying ratios of organ activities according to an experimental time activity curve and created dynamic sinograms. The sinogram data were reconstructed by filtered backprojection. By comparing a scatter-corrected image (SC) with a true image (TRUE), we evaluated the accuracy of the scatter correction. TRUE was reconstructed using a scatter-eliminated sinogram, which can be obtained only in simulations. A scatter-uncorrected image (W/O SC) and an attenuation-uncorrected image (W/O AC) were also constructed. Finally, we calculated MBF and PTF with a single tissue-compartment model for four types of images. As a result, scatter was corrected accurately, and MBFs derived from all types of images were consistent with the MBF obtained from TRUE. Meanwhile, the PTF of only the SC was in agreement with the PTF of TRUE. From the simulation results, we concluded that quantitative MBF is less affected by scatter and absorption in 3D-PET using (15)O-water. However, scatter correction is essential for accurate PTF.

Purpose: Recently, photomultiplier tubes (PMTs) and position sensitive PMTs (PSPMTs) with higher quantum efficiencies (HQE) have been developed. However, it remains unclear whether they actually improve such performances as the energy and spatial resolution for PET and SPECT detectors., Methods: The authors evaluated the quantum efficiencies (QEs) for PMTs and PSPMTs and measured the energy resolution of a 3-in. round HQE PMT combined with various scintillators and compared the results with a conventional normal quantum efficiency (NQE) PMT of the same type. The authors also measured the position and energy performance of a 2-in. square HQE PSPMT combined with scintillator blocks and compared them with a NQE PSPMT of the same size., Results: The energy resolution of the 3-in. round HQE PMT showed higher energy resolution than the NQE with all scintillators. The improvement of the energy resolution was smaller, for all measurements, than the expected value from the quantum efficiency of the PMT but was higher for the scintillators with smaller light outputs. The energy and position performance of the HQE PSPMT based block detectors showed higher position and energy performance than those with NQE., Conclusions: From these results, the authors conclude that both HQE PMT and PSPMT contribute to improve the energy and position performance for PET and SPECT detectors. Significant performance improvements will be expected in PET and SPECT systems by the use of the HQE PMTs or PSPMTs.

Purpose: The simultaneous measurement of PET and magnetic resonance imaging (MRI) is an emerging field for molecular imaging research. Although optical fiber based PET∕MRI systems have advantages on less interference between PET and MRI, there is a drawback in reducing the scintillation light due to the fiber. To reduce the problem, the authors newly developed flexible optical fiber bundle based block detectors and employed them for a high resolution integrated PET∕MRI system., Methods: The flexible optical fiber bundle used 0.5 mm diameter, 80 cm long double clad fibers which have dual 12 mm × 24 mm rectangular inputs and a single 24 mm × 24 mm rectangular output. In the input surface, LGSO scintillators of 0.025 mol.% (decay time: ∼31 ns: 0.9 mm × 1.3 mm × 5 mm) and 0.75 mol.% (decay time: ∼46 ns: 0.9 mm × 1.3 mm × 6 mm) were optically coupled in depth direction to form depth-of-interaction detector, arranged in 11 × 13 matrix and optically coupled to the fiber bundle. The two inputs of the bundle are bent for 90°, bound to one, and are optically coupled to a Hamamatsu 1-in. square position sensitive photomultiplier tube., Results: Light loss due to the fiber bundle could be reduced and the performance of the block detectors was improved. Eight optical fiber based block detectors (16 LGSO blocks) were arranged in a 56 mm diameter ring to form a PET system. Spatial resolution and sensitivity were 1.2 mm full-width at half-maximum and 1.2% at the central field-of-view, respectively. Sensitivity change was less than 1% for 2 °C temperature changes. This PET system was integrated with a 0.3 T permanent magnet MRI system which has 17 cm diameter hole at the yoke area for insertion of the PET detector ring. There was no observable interference between PET and MRI. Simultaneous imaging of PET and MRI was successfully performed for small animal studies., Conclusions: The authors confirmed that the developed high resolution PET∕MRI system is promising for molecular imaging research.

Introduction: Measurement of regional cerebral blood flow (rCBF) in rodents can provide knowledge of pathophysiology of the cerebral circulation, but generally requires blood sampling for analysis during positron emission tomography (PET). We therefore tested the feasibility of using an arteriovenous (AV) shunt in rats for less invasive blood analysis., Methods: Six anesthetized rats received [15O]H2O and [15O]CO PET scans with their femoral artery and vein connected by an AV shunt, the activity within which was measured with a germanium ortho-oxysilicate scintillation detector. The [15O]H2O was intravenously injected either at a faster or slower injection rate, while animals were placed either with their head or heart centered in the gantry. The time-activity curve (TAC) from the AV shunt was compared with that from the cardiac ventricle in PET image. The rCBF values were calculated by a nonlinear least-square method using the dispersion-corrected AV-shunt TAC as an input., Results: The AV-shunt TAC had higher signal-to-noise ratio, but also had delay and dispersion compared with the image-derived TAC. The delay time between the AV-shunt TAC and image-based TAC ranged from 11 to 21 s, while the dispersion was estimated to be ∼5 s as a time constant of the dispersion model of exponential function, and both were properly corrected. In a steady-state condition of [15O]CO PET, the blood activity concentration by AV-shunt TAC was also comparable in height with the image-based TAC corrected for partial volume. Whole-brain CBF values measured by [15O]H2O were 0.37±0.04 (mean±S.D.) ml/g/min, partition coefficient was 0.73±0.04 ml/g, and the CBF varied in a linear relationship with partial pressure of carbon dioxide during each scan., Conclusions: The AV-shunt technique allows less invasive, quantitative and reproducible measurement of rCBF in [15O]H2O PET studies in rats than direct blood sampling and radioassay., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Patient movement has been considered an important source of errors in cardiac PET. This study was aimed at evaluating the effects of such movement on myocardial blood flow (MBF) and perfusable tissue fraction (PTF) measurements in intravenous ¹⁵O-water PET., Methods: Nineteen ¹⁵O-water scans were performed on ten healthy volunteers and three patients with severe cardiac dysfunction under resting conditions. Motions of subjects during scans were estimated by monitoring locations of markers on their chests using an optical motion-tracking device. Each sinogram of the dynamic emission frames was corrected for subject motion. Variation of regional MBF and PTF with and without the motion corrections was evaluated., Results: In nine scans, motions during ¹⁵O-water scan (inter-frame (IF) motion) and misalignments relative to the transmission scan (inter-scan (IS) motion) larger than the spatial resolution of the PET scanner (4.0 mm) were both detected by the optical motion-tracking device. After correction for IF motions, MBF values changed from 0.845 ± 0.366 to 0.780 ± 0.360 mL/minute/g (P < .05). In four scans with only IS motion detected, PTF values changed significantly from 0.465 ± 0.118 to 0.504 ± 0.087 g/mL (P< .05), but no significant change was found in MBF values., Conclusions: This study demonstrates that IF motion during ¹⁵O-water scan at rest can be source of error in MBF measurement. Furthermore, estimated MBF is less sensitive than PTF values to misalignment between transmission and ¹⁵O-water emission scans.

Objective: Gastrointestinal stromal tumors (GISTs) and malignant lymphomas (MLs) in the abdomen are often observed as tumors of unknown origin on F-18 FDG PET/CT. The purpose of this study was to evaluate the intratumoral metabolic heterogeneity of F-18 FDG uptake on PET to determine if it might be helpful to discriminate between these tumors., Methods: The F-18 FDG PET/CT findings of 21 large abdominal tumors were retrospectively evaluated (9 GISTs and 12 MLs). Intratumoral heterogeneity was evaluated by visual scoring (visual score: 0, homogeneous; 1, slightly heterogeneous; 2, moderately heterogeneous; 3, highly heterogeneous) and by the cumulative standardized uptake value (SUV) histograms on transaxial PET images at the maximal cross-sectional tumor diameter. Percent tumor areas above a threshold from 0 to 100% of the maximum SUV were plotted and the area under curve of the cumulative SUV histograms (AUC-CSH) was used as a heterogeneity index, where lower values corresponded with increased heterogeneity. Correlation between the visual score and the AUC-CSH was investigated by the Spearman's rank test., Results: GISTs exhibited heterogeneous uptake of F-18 FDG, whereas MLs showed rather homogeneous uptake on visual analysis (visual score: 2.67 ± 0.50 and 0.58 ± 0.79, respectively; p < 0.001). The AUC-CSH was significantly lower for the GISTs than for the MLs (0.41 ± 0.14 and 0.64 ± 0.08, respectively; p < 0.001). Significant correlations were observed between the visual score and the AUC-CSH (ρ = -0.866, p < 0.001)., Conclusion: GISTs exhibited significantly heterogeneous intratumoral tracer uptake as compared with the MLs. Evaluation of the intratumoral heterogeneity of F-18 FDG uptake may help in the discrimination between these tumors.

The silicon photomultiplier (Si-PM) is a promising photo-detector for PET for use in magnetic resonance imaging (MRI) systems because it has high gain and is insensitive to static magnetic fields. Recently we developed a Si-PM-based depth-of-interaction PET system for small animals and performed simultaneous measurements by combining the Si-PM-based PET and the 0.15 T permanent MRI to test the interferences between the Si-PM-based PET and an MRI. When the Si-PM was inside the MRI and installed around the radio frequency (RF) coil of the MRI, significant noise from the RF sequence of the MRI was observed in the analog signals of the PET detectors. However, we did not observe any artifacts in the PET images; fluctuation increased in the count rate of the Si-PM-based PET system. On the MRI side, there was significant degradation of the signal-to-noise ratio (S/N) in the MRI images compared with those without PET. By applying noise reduction procedures, the degradation of the S/N was reduced. With this condition, simultaneous measurements of a rat brain using a Si-PM-based PET and an MRI were made with some degradation in the MRI images. We conclude that simultaneous measurements are possible using Si-PM-based PET and MRI.

In quantitative measurements of small animal PET studies, blood sampling is limited due to the small amounts of blood such animals can provide. In addition, injection doses are quite limited. In this situation, a high-sensitivity well counter would be useful for reducing the amount of the blood sample needed from small animals. Bismuth germinate (BGO) has a high stopping power for high-energy gamma rays compared to NaI(Tl), which is commonly used for conventional well counters. We have developed a BGO well counter and have tested it for blood-sampling measurements in small animals. The BGO well counter uses a square BGO block (59 × 59 × 50 mm) with a square open space (27 × 27 × 34 mm) in the center of the block. The BGO block was optically coupled to a 59-mm square-shaped photomultiplier tube (PMT). Signals from the PMT were digitally processed for the integration and energy window setting. The results showed that the energy spectrum of the BGO well counter measured with a Na-22 point source provided counts that were about 6 times higher for a 1022-keV (511 keV × 2) gamma peak than the spectrum of a 2-in. NaI(Tl) well counter. The relative sensitivity of the developed BGO well counter was 3.4 times higher than that of a NaI(Tl) well counter. The time activity curve of arterial blood was obtained successfully with the BGO well counter for a F-18-FDG study on rat. The BGO well counter will contribute to reducing the amount of sampled blood and to improving the throughput of quantitative measurements in small animal PET studies.

A silicon photomultiplier (Si-PM) is a promising photodetector for PET, especially for PET/MRI combined systems, due to its high gain, small size, and lower sensitivity to static magnetic fields. However, these properties are also promising for gamma camera systems for single-photon imaging. We developed an ultra-high-resolution Si-PM-based compact gamma camera system for small animals. Y(2)SiO(5):Ce (YSO) was selected as scintillators because of its high light output and no natural radioactivity. The gamma camera consists of 0.6 mm × 0.6 mm × 6 mm YSO pixels combined with a 0.1 mm thick reflector to form a 17 × 17 matrix that was optically coupled to a Si-PM array (Hamamatsu multi-pixel photon counter S11064-050P) with a 2 mm thick light guide. The YSO block size was 12 mm × 12 mm. The YSO gamma camera was encased in a 5 mm thick gamma shield, and a parallel hole collimator was mounted in front of the camera (0.5 mm hole, 0.7 mm separation, 5 mm thick). The two-dimensional distribution for the Co-57 gamma photons (122 keV) was almost resolved. The energy resolution was 24.4% full-width at half-maximum (FWHM) for the Co-57 gamma photons. The spatial resolution at 1.5 mm from the collimator surface was 1.25 mm FWHM measured using a 1 mm diameter Co-57 point source. Phantom and small animal images were successfully obtained. We conclude that a Si-PM-based gamma camera is promising for molecular imaging research.

The silicon photomultiplier (Si-PM) is a promising photodetector for a high-resolution PET scanner due to its small size, high gain and lower sensitivity to magnetic fields. There are several commercially available Si-PM arrays with different pixel sizes and fill factors, and these parameters can affect the performance of a PET block detector read out by these devices. We compared the performance of block detectors using 4 × 4 Si-PM arrays with 25 µm (Hamamatsu S11064-025P) and 50 µm (S11064-050P) pixels combined with the same 15 × 15 matrix LGSO block made of 0.7 × 0.7 × 6 mm(3) scintillator pixels. Evaluated characteristics include photopeak linearity, energy resolution and positioning performance. Although the photopeak linearity and energy resolution are slightly better for the Si-PM with 25 µm pixels, the position performance measured by the separation of the position histogram is significantly better for the Si-PM with 50 µm pixels. We conclude that using the Si-PM with 50 µm pixels will provide a better solution for the development of ultrahigh-resolution PET systems.

Quantitative interpretation of brain [¹⁸F]FDOPA PET data has been made possible by several kinetic modeling approaches, which are based on different assumptions about complex [¹⁸F]FDOPA metabolic pathways in brain tissue. Simple kinetic macro parameters are often utilized to quantitatively evaluate metabolic and physiological processes of interest, which may include DDC activity, vesicular storage, and catabolism from (18) F-labeled dopamine to DOPAC and HVA. A macro parameter most sensitive to the changes of these processes would be potentially beneficial to identify impaired processes in a neurodegenerative disorder such as Parkinson's disease. The purpose of this study is a systematic comparison of several [¹⁸F]FDOPA macro parameters in terms of sensitivities to process-specific changes in simulated time-activity curve (TAC) data of [¹⁸F]FDOPA PET. We introduced a multiple-compartment kinetic model to simulate PET TACs with physiological changes in the dopamine pathway. TACs in the alteration of dopamine synthesis, storage, and metabolism were simulated with a plasma input function obtained by a non-human primate [¹⁸F]FDOPA PET study. Kinetic macro parameters were calculated using three conventional linear approaches (Gjedde-Patlak, Logan, and Kumakura methods). For simulated changes in dopamine storage and metabolism, the slow clearance rate (k(loss) ) as calculated by the Kumakura method showed the highest sensitivity to these changes. Although k(loss) performed well at typical ROI noise levels, there was large bias at high noise level. In contrast, for simulated changes in DDC activity it was found that K(i) and V(T), estimated by Gjedde-Patlak and Logan method respectively, have better performance than k(loss)., (Copyright © 2011 Wiley-Liss, Inc.)

The silicon-photomultiplier (Si-PM) is a promising photodetector, especially for integrated PET/MRI systems, due to its small size, high gain, and low sensitivity to static magnetic fields. The major problem using a Si-PM-based PET system within the MRI system is the interference between the PET and MRI units. We measured the interference by combining a Si-PM-based PET system with a permanent-magnet MRI system. When the RF signal-induced pulse height exceeded the lower energy threshold level of the PET system, interference between the Si-PM-based PET system and MRI system was detected. The prompt as well as the delayed coincidence count rates of the Si-PM-based PET system increased significantly. These noise counts produced severe artifacts on the reconstructed images of the Si-PM-based PET system. In terms of the effect of the Si-PM-based PET system on the MRI system, although no susceptibility artifact was observed on the MR images, electronic noise from the PET detector ring was detected by the RF coil and reduced the signal-to-noise ratio (S/N) of the MR images. The S/N degradation of the MR images was reduced when the distance between the RF coil and the Si-PM-based PET system was increased. We conclude that reducing the interference between the PET and MRI systems is essential for achieving the optimum performance of integrated Si-PM PET/MRI systems.

The silicon-photomultiplier (Si-PM) is a promising photodetector for the development of new PET systems due to its small size, high gain and relatively low sensitivity to the static magnetic field. One drawback of the Si-PM is that it has significant temperature-dependent gain that poses a problem for the stability of the Si-PM-based PET system. To reduce this problem, we developed and tested a temperature-dependent gain control system for the Si-PM-based PET system. The system consists of a thermometer, analog-to-digital converter, personal computer, digital-to-analog converter and variable gain amplifiers in the weight summing board of the PET system. Temperature characteristics of the Si-PM array are measured and the calculated correction factor is sent to the variable gain amplifier. Without this correction, the temperature-dependent peak channel shifts of the block detector were -55% from 20 °C to 35 °C. With the correction, the peak channel variations were corrected within ±8%. The coincidence count rate of the Si-PM-based PET system was measured using a Na-22 point source while monitoring the room temperature. Without the correction, the count rate inversely changed with the room temperature by 10% for 1.5° C temperature changes. With the correction, the count rate variation was reduced to within 3.7%. These results indicate that the developed temperature-dependent gain control system can contribute to improving the stability of Si-PM-based PET systems.

A Geiger-mode avalanche photodiode (Si-PM) is a promising photodetector for PET, especially for use in a magnetic resonance imaging (MRI) system, because it has high gain and is less sensitive to a static magnetic field. We developed a Si-PM-based depth-of-interaction (DOI) PET system for small animals. Hamamatsu 4 × 4 Si-PM arrays (S11065-025P) were used for its detector blocks. Two types of LGSO scintillator of 0.75 mol% Ce (decay time: ∼45 ns; 1.1 mm × 1.2 mm × 5 mm) and 0.025 mol% Ce (decay time: ∼31 ns; 1.1 mm × 1.2 mm × 6 mm) were optically coupled in the DOI direction to form a DOI detector, arranged in a 11 × 9 matrix, and optically coupled to the Si-PM array. Pulse shape analysis was used for the DOI detection of these two types of LGSOs. Sixteen detector blocks were arranged in a 68 mm diameter ring to form the PET system. Spatial resolution was 1.6 mm FWHM and sensitivity was 0.6% at the center of the field of view. High-resolution mouse and rat images were successfully obtained using the PET system. We confirmed that the developed Si-PM-based PET system is promising for molecular imaging research.

Purpose: Cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of O(2) (CMRO(2)) can be quantified by PET with the administration of H (2) (15) O and (15)O(2). Recently, a shortening in the duration of these measurements was achieved by the sequential administration of dual tracers of (15)O(2) and H (2) (15) O with PET acquisition and integration method (DARG method). A transmission scan is generally required for correcting photon attenuation in advance of PET scan. Although the DARG method can shorten the total study duration to around 30 min, the transmission scan duration has not been optimized and has possibility to shorten its duration. Our aim of this study was to determine the optimal duration for the transmission scan. We introduced 'N-index', which estimates the noise level on an image obtained by subtracting two statistically independent and physiologically equivalent images. The relationship between noise on functional images and duration of the transmission scan was investigated by N-index., Methods: We performed phantom studies to test whether the N-index reflects the pixel noise in a PET image. We also estimated the noise level by the N-index on CBF, OEF and CMRO(2) images from DARG method in clinical patients, and investigated an optimal true count of the transmission scan., Results: We found tight correlation between pixel noise and N-index in the phantom study. By investigating relationship between the transmission scan duration and N-index value for the functional images by DARG method, we revealed that the transmission data with true counts of more than 40 Mcounts results in CBF, OEF, and CMRO(2) images of reasonable quantitative accuracy and quality., Conclusion: The present study suggests that further shortening of DARG measurement is possible by abridging the transmission scan. The N-index could be used to determine the optimal measurement condition when examining the quality of image.

Purpose: Although (15)O-O(2) gas inhalation can provide a reliable and accurate myocardial metabolic rate for oxygen by PET, the spillover from gas volume in the lung distorts the images. Recently, we developed an injectable method in which blood takes up (15)O-O(2) from an artificial lung, and this made it possible to estimate oxygen metabolism without the inhalation protocol. In the present study, we evaluated the effectiveness of the injectable (15)O-O(2) system in porcine hearts., Methods: PET scans were performed after bolus injection and continuous infusion of injectable (15)O-O(2) via a shunt between the femoral artery and the vein in normal pigs. The injection method was compared to the inhalation method. The oxygen extraction fraction (OEF) in the lateral walls of the heart was calculated by a compartmental model in view of the spillover and partial volume effect., Results: A significant decrease of lung radioactivity in PET images was observed compared to the continuous inhalation of (15)O-O(2) gas. Furthermore, the injectable (15)O-O(2) system provides a measurement of OEF in lateral walls of the heart that is similar to the continuous-inhalation method (0.71 +/- 0.036 and 0.72 +/- 0.020 for the bolus-injection and continuous-infusion methods, respectively)., Conclusion: These results indicate that injectable (15)O-O(2) has the potential to evaluate myocardial oxygen metabolism.

Objective: Cardiac (15)O-water PET studies provide an accurate quantitation of regional myocardial blood flow (rMBF). We developed a motion correction system using an optical motion-tracking device to detect a subject's global movement for cardiac study., Methods: PET studies were carried out on a cardiac phantom and a healthy volunteer at rest. The three-dimensional locations of the markers attached to the subjects during scans were measured using an optical motion-tracking system. In the phantom study, we performed a transmission scan and seven (18)F emission scans of a baseline and with artificial misalignment of shifts and rotations. The correlation coefficients between the baseline and the other images before and after the corrections for the misalignment were calculated. In the human study, we performed a (15)O-water dynamic scan with a transmission and axially 30 mm-shifted transmission scans. Motion of the subject was estimated by the information from the system, and was corrected on each sinogram using attenuation maps realigned to dynamic frames. Reconstructed dynamic images were then realigned to the transmission data. We calculated rMBF values for nine segments and myocardial images from the emission images, which were reconstructed with the first attenuation map (reference) and with the misaligned attenuation map before and after our corrections., Results: In the phantom study, the correlation coefficients were improved from 0.929 +/- 0.022 to 0.987 +/- 0.010 (mean +/- SD) after the corrections. In the human study, the global and cyclic movements were detected. The cyclic movement due to respiration was smoothed by frame-averaging, and reasonable information of the global movement was obtained. The rMBF value (mean +/- SD) was 0.94 +/- 0.12 mL/min/g for the reference. The rMBF values using the misaligned attenuation map changed from 1.03 +/- 0.21 to 0.93 +/- 0.11 mL/min/g after the correction, and spurious defects in myocardial images were also recovered., Conclusions: Our technique provided reasonable information for correcting the global movement of the subject. It was shown that this system was applicable to detect and correct subject movement in cardiac PET studies at rest.

The aim of this study was to establish kinetic analysis of [5-(11)C-methoxy]donepezil ([(11)C]donepezil), which was developed for the in-vivo visualization of donepezil binding to acetylcholinesterase (AChE) using positron emission tomography (PET). Donepezil is an AChE inhibitor that is widely prescribed to ameliorate the cognitive impairment of patients with dementia. Six healthy subjects took part in a dynamic study involving a 60-min PET scan after intravenous injection of [(11)C]donepezil. The total distribution volume (tDV) of [(11)C]donepezil was quantified by compartmental kinetic analysis and Logan graphical analysis. A one-tissue compartment model (1TCM) and a two-tissue compartment model (2TCM) were applied in the kinetic analysis. Goodness of fit was assessed with chi(2) criterion and Akaike's Information Criterion (AIC). Compared with a 1TCM, goodness of fit was significantly improved by a 2TCM. The tDVs provided by Logan graphical analysis were slightly lower than those provided by a 2TCM. The rank order of the mean tDVs in 10 regions was in line with the AChE activity reported in a previous post-mortem study. Logan graphical analysis generated voxel-wise images of tDV, revealing the overall distribution pattern of AChE in individual brains. Significant correlation was observed between tDVs calculated with and without metabolite correction for plasma time-activity curves, indicating that metabolite correction could be omitted. In conclusion, this method enables quantitative analysis of AChE and direct investigation of the pharmacokinetics of donepezil in the human brain.

Cerebral metabolic rate of oxygen (CMRO(2)) can be assessed quantitatively using (15)O(2) and positron emission tomography. Determining the arterial input function is considered critical with regards to the separation of the metabolic product of (15)O(2) (RW) from a measured whole blood. A mathematical formula based on physiologic model has been proposed to predict RW. This study was intended to verify the adequacy of that model and a simplified procedure applying that model for wide range of species and physiologic conditions. The formula consists of four parameters, including of a production rate of RW (k) corresponding to the total body oxidative metabolism (BMRO(2)). Experiments were performed on 6 monkeys, 3 pigs, 12 rats, and 231 clinical patients, among which the monkeys were studied at varied physiologic conditions. The formula reproduced the observed RW. Greater k values were observed in smaller animals, whereas other parameters did not differ amongst species. The simulation showed CMRO(2) sensitive only to k, but not to others, suggesting that validity of determination of only k from a single blood sample. Also, k was correlated with BMRO(2), suggesting that k can be determined from BMRO(2). The present model and simplified procedure can be used to assess CMRO(2) for a wide range of conditions and species.

Positron emission tomography dynamic studies have been performed to quantify several biomedical functions. In a quantitative analysis of these studies, kinetic parameters were estimated by mathematical methods, such as a nonlinear least-squares algorithm with compartmental model and graphical analysis. In this estimation, the uncertainty in the estimated kinetic parameters depends on the signal-to-noise ratio and quantitative analysis method. This review describes the reliability of parameter estimates for various analysis methods in reversible and irreversible models.

Physiological functions (e.g., cerebral blood flow, glucose metabolism, and neuroreceptor binding) can be investigated as parameters estimated by kinetic modeling using dynamic positron emission tomography (PET) images. Imaging of these physiological parameters, called parametric imaging, can locate the regional distribution of functionalities. However, the most serious technical issue affecting parametric imaging is noise in dynamic PET data. This review describes wavelet denoising of dynamic PET images for improving image quality in estimated parametric images. Wavelet denoising provides significantly improved quality directly to dynamic PET images and indirectly to estimated parametric images. The application of wavelet denoising to radio-ligand and kinetic analysis is still in the development stage, but even so, it is thought that wavelet techniques will have a substantial impact on nuclear medicine in the near future.

Cerebral metabolic rate of oxygen (CMRO(2)), oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images can be quantified using positron emission tomography (PET) by administrating (15)O-labelled water (H(15)(2)O) and oxygen ((15)O(2)). Conventionally, those images are measured with separate scans for three tracers C(15)O for CBV, H(15)(2)O for CBF and (15)O(2) for CMRO(2), and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach (Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO(2) rapidly by sequentially administrating H(15)(2)O and (15)O(2) within a short time. Because quantitative CBF and CMRO(2) values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time-activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model-based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO(2) were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO(2) values by the DARG approach did not exceed the acceptable range, i.e., errors in those values were within 5%, when the area under the curve in the input function of the second tracer was larger than half of the first one. Bias and deviation in those values were also compatible to that of the conventional method, when noise was imposed on the arterial TAC. We concluded that the present calculation based methods could be of use for quantitatively calculating CBF and CMRO(2) with the DARG approach.

The Logan plot is a widely used algorithm for the quantitative analysis of neuroreceptors using PET because it is easy to use and simple to implement. The Logan plot is also suitable for receptor imaging because its algorithm is fast. However, use of the Logan plot, and interpretation of the formed receptor images should be regarded with caution, because noise in PET data causes bias in the Logan plot estimates. In this paper, we describe the basic concept of the Logan plot in detail and introduce three algorithms for the Logan plot. By comparing these algorithms, we demonstrate the pitfalls of the Logan plot and discuss the solution.

The threshold of cerebral blood flow (CBF) into infarction in rats has been indicated to be similar to that in patients. However, CBF does not reflect metabolic function, and so estimations of oxygen metabolism have been required. Here, we estimated changes in oxygen metabolism after occluding the right middle cerebral artery (MCA) in rats using an injectable (15)O-O(2) we developed. A decrease in CBF (left: 0.67+/-0.22 mL/min/g, right: 0.44+/-0.17 mL/min/g, P<0.05) and compensatory increase in the oxygen extraction fraction (OEF) (left: 0.42+/-0.13, right: 0.50+/-0.19, P<0.05) were observed at 1-h after occlusion. In contrast, a marked decrease in CBF and the cerebral metabolic rate for oxygen and a collapse of the compensatory OEF mechanism were found at 24 h after occlusion. Injectable (15)O-O(2) could be used to reliably estimate oxygen metabolism in an infarction rat model with positron emission tomography.

PET enables not only visualization of the distribution of radiotracer, but also has ability to quantify several biomedical functions. Compartmental model is a basic idea to analyze dynamic PET data. This review describes the principle of the compartmental model and categorizes the techniques and approaches for the compartmental model according to various aspects: model design, experimental design, invasiveness, and mathematical solution. We also discussed advanced applications of the compartmental analysis with PET.

Recently, list mode (event-by-event) data acquisition with positron emission tomography (PET) has been widely noticed because list mode acquisition is superior to conventional frame mode data acquisition in terms of (1) higher efficiency of data storage, (2) higher temporal resolution, and (3) higher flexibility of data manipulation. The aim of this study is to investigate the performance of list mode data acquisition with ECAT EXACT HR and HR+ PET scanners (CTI PET Systems) and its feasibility in clinical applications. A cylindrical phantom (16 cm in diameter and length) filled with a 11C solution for the HR and a 15O solution for the HR+ was scanned several times by varying the radioactivity concentration with the list mode and frame mode acquisitions. The scans were also carried out with a septa (2D mode) and without a septa (3D mode) in order to evaluate the effect of the interplane septa on the quality of the list mode data. The acquired list mode data were sorted into a sinogram and reconstructed using a filtered back-projection algorithm. The count rate performance of the list mode data was comparable to that of the frame mode data. However, the list mode acquisition could not be performed when the radioactivity concentration in the field-of-view was high (exceeding 24 kBq/ml for the 3D mode) due to a lack of sufficient transfer speed for sending data from the memory to hard disk. In order to estimate the pixel noise in a reconstructed image, ten replicated data sets were generated from one list mode data. The reconstructed images with the 3D mode had a signal-to-noise ratio that was more than 60% better than that of the image with the 2D mode. The file size of the generated list mode data was also evaluated. In the case of ECAT EXACT HR+ with the 3D list mode, the list mode data with a generated file size of 2.31 Mbytes/ s were generated for 37 MBq injections. Our results suggest that careful attention must be paid to the protocol of the list mode data acquisition in order to obtain the highest performance of the PET scanner.

Recently, small animal imaging by pinhole SPECT has been widely investigated by several researchers. We developed a pinhole SPECT system specially designed for small animal imaging. The system consists of a rotation unit for a small animal and a SPECT camera attached with a pinhole collimator. In order to acquire complete data of the projections, the system has two orbits with angles of 90 degrees and 45 degrees with respect to the object. In this system, the position of the SPECT camera is kept fixed, and the animal is rotated in order to avoid misalignment of the center of rotation (COR). We implemented a three dimensional OSEM algorithm for the reconstruction of data acquired by the system from both the orbitals. A point source experiment revealed no significant COR misalignment using the proposed system. Experiments with a line phantom clearly indicated that our system succeeded in minimizing the misalignment of the COR. We performed a study with a rat and 99mTc-HMDP, an agent for bone scan, and demonstrated a dramatic improvement in the spatial resolution and uniformity achieved by our system in comparison with the conventional Feldkamp algorithm with one set of orbital data.

The aim of the present study is to evaluate the validity of the simplified reference tissue model (SRTM) and of Logan graphical analysis with reference tissue (LGAR) for quantification of histamine H1 receptors (H1Rs) by using positron emission tomography (PET) with [11C]doxepin. These model-based analytic methods (SRTM and LGAR) are compared to Logan graphical analysis (LGA) and to the one-tissue model (1TM), using complete datasets obtained from 5 healthy volunteers. Since HIR concentration in the cerebellum can be regarded as negligibly small, the cerebellum was selected as the reference tissue in the present study. The comparison of binding potential (BP) values estimated by LGAR and 1TM showed good agreement; on the other hand, SRTM turned out to be unstable concerning parameter estimation in several regions of the brain. By including the results of noise analysis, LGAR became a reliable method for parameter estimation of [11C]doxepin data in the cortical regions.

Unlabelled: Regional myocardial blood flow (MBF) can be measured with 15O-water and PET using the 1-tissue-compartment model with perfusable tissue fraction, which provides an MBF value that is free from the partial-volume effect. Studies with 15O-water have several advantages, such as the ability to repeat a scan. However, because of the short scanning time and the small distribution volume of 15O-water in the myocardium, the image quality of 15O-water is limited, impeding the computation of MBF and perfusable tissue fraction at the voxel level. We implemented the basis function method for generating parametric images of MBF, perfusable tissue fraction, and arterial blood volume (Va) with 15O-water and PET. The basis function method linearizes the solution of the 1-tissue-compartment model, which results in a computationally much faster method than the conventional nonlinear least-squares fitting method in estimating the parameters., Methods: To validate the basis function method, we performed a series of PET studies on miniature pigs (n = 7). After acquisition of the transmission scan for attenuation correction and the 15O-CO scan for obtaining the blood-pool image, repeated PET scans with 15O-water were obtained with varying doses of adenosine or CGS-21680 (selective adenosine A(2a) receptor agonist). MBF, perfusable tissue fraction, and Va values of the myocardial region for each scan were computed using the basis function method and the nonlinear least-squares method, and the parameters estimated by the 2 methods were compared., Results: MBF images generated by the basis function method demonstrated an increase in blood flow after administration of adenosine or CGS-21680. The MBF values estimated by the basis function method and by the nonlinear least-squares method correlated strongly., Conclusion: The basis function method produces parametric images of MBF, perfusable tissue fraction, and Va with 15O-water and PET. These images will be useful in detecting regional myocardial perfusion abnormalities.