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SPECT can provide valuable diagnostic and treatment response information in large-scale multicenter clinical trials. However, SPECT has been limited in providing consistent quantitative functional parametric values across the centers, largely because of a lack of standardized procedures to correct for attenuation and scatter. Recently, a novel software package has been developed to reconstruct quantitative SPECT images and assess cerebral blood flow (CBF) at rest and after acetazolamide challenge from a single SPECT session. This study was aimed at validating this technique at different institutions with a variety of SPECT devices and imaging protocols. Methods: Twelve participating institutions obtained a series of SPECT scans on physical phantoms and clinical patients. The phantom experiments included the assessment of septal penetration for each collimator used and of the accuracy of the reconstructed images. Clinical studies were divided into 3 protocols, including intrainstitutional reproducibility, a comparison with PET, and rest-rest study consistency. The results from 46 successful studies were analyzed. Results: Activity concentration estimation (Bq/mL) in the reconstructed SPECT images of a uniform cylindric phantom showed an interinstitution variation of 65.1%, with a systematic underestimation of concentration by 12.5%. CBF values were reproducible both at rest and after acetazolamide on the basis of repeated studies in the same patient (mean 6 SD difference, 20.4 6 5.2 mL/min/100 g, n 5 44). CBF values were also consistent with those determined using PET (26.1 6 5.1 mL/min/100 g, n 5 6). Conclusion: This study demonstrates that SPECT can quantitatively provide physiologic functional images of rest and acetazolamide challenge CBF, using a quantitative reconstruction software package.Key Words: 123 I-iodoamphetamine; cerebral blood flow; acetazolamide; SPECT; vascular reactivity; quantitation J Nucl Med 2010; 51: 1624 -1631 DOI: 10.2967 Current clinical practice using SPECT relies largely on interpretation of qualitative images reflecting physiologic function. Quantitative functional parametric images may be obtained by applying mathematic modeling to SPECT data corrected for attenuation and scatter. Quantitative regional cerebral blood flow (CBF) (1-3) and cerebral vascular reactivity (CVR) in response to acetazolamide challenge (4-6) have been obtained with these techniques. One major application of such quantitative SPECT (QSPECT) approaches is the evaluation of ischemic status in patients with occlusion or stenosis in their middle cerebral arteries, to provide prognostic information of the outcome of revascularization therapies (7). Quantitative analysis in SPECT has also been demonstrated in the assessment of binding potential for several neuroreceptor ligands (8,9), for the quantitative assessment of regional myocardial perfusion (10,11), and for the assessment of radioaerosol deposition and clearance in healthy and diseased lungs (12). However, providing the standardized quantitative approach...

IntroductionA physical 3-dimensional phantom that simulates PET/SPECT images of static regional cerebral blood flow in grey matter with a realistic head contour has been developed. This study examined the feasibility of using this phantom for evaluating PET/SPECT images.MethodsThe phantom was constructed using a transparent, hydrophobic photo-curable polymer with a laser-modelling technique. The phantom was designed to contain the grey matter, the skull, and the trachea spaces filled with a radioactive solution, a bone-equivalent solution of K2HPO4, and air, respectively. The grey matter and bone compartments were designed to establish the connectivity. A series of experiments was performed to confirm the accuracy and reproducibility of the phantom using X-ray CT, SPECT, and PET.ResultsThe total weight was 1997 ± 2 g excluding the inner liquid, and volumes were 563 ± 1 and 306 ± 2 mL, corresponding to the grey matter and bone compartments, respectively. The apparent attenuation coefficient averaged over the whole brain was 0.168 ± 0.006 cm−1 for Tc-99 m, which was consistent with the previously reported value for humans (0.168 ± 0.010 cm−1). Air bubbles were well removed from both grey-matter and bone compartments, as confirmed by X-ray CT. The phantom was well adapted to experiments using PET and SPECT devices.ConclusionThe 3-dimensional brain phantom constructed in this study may be of use for evaluating the adequacy of SPECT/PET reconstruction software programs.

Positron emission tomography (PET) with 15O 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 (CMRO2). However, most of techniques require an additional C15O 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 H215O and 15O2. 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 CMRO2. A simulation study demonstrated similar error propagation between DBFM and DARG. The DBFM method enables accurate assessment of CBF and CMRO2 without additional CBV scan within significantly shortened examination period, in clinical settings.

Even as medical data sets become more publicly accessible, most are restricted to specific medical conditions. Thus, data collection for machine learning approaches remains challenging, and synthetic data augmentation, such as generative adversarial networks (GAN), may overcome this hurdle. In the present quality control study, deep convolutional GAN (DCGAN)–based human brain magnetic resonance (MR) images were validated by blinded radiologists. In total, 96 T1-weighted brain images from 30 healthy individuals and 33 patients with cerebrovascular accident were included. A training data set was generated from the T1-weighted images and DCGAN was applied to generate additional artificial brain images. The likelihood that images were DCGAN-created versus acquired was evaluated by 5 radiologists (2 neuroradiologists [NRs], vs 3 non-neuroradiologists [NNRs]) in a binary fashion to identify real vs created images. Images were selected randomly from the data set (variation of created images, 40%–60%). None of the investigated images was rated as unknown. Of the created images, the NRs rated 45% and 71% as real magnetic resonance imaging images (NNRs, 24%, 40%, and 44%). In contradistinction, 44% and 70% of the real images were rated as generated images by NRs (NNRs, 10%, 17%, and 27%). The accuracy for the NRs was 0.55 and 0.30 (NNRs, 0.83, 0.72, and 0.64). DCGAN-created brain MR images are similar enough to acquired MR images so as to be indistinguishable in some cases. Such an artificial intelligence algorithm may contribute to synthetic data augmentation for “data-hungry” technologies, such as supervised machine learning approaches, in various clinical applications.

Effective delivery of drug carriers selectively to the kidney is challenging because of their uptake by the reticuloendothelial system in the liver and spleen, which limits effective treatment of kidney diseases and results in side effects. To address this issue, we synthesized L-serine (Ser)-modified polyamidoamine dendrimer (PAMAM) as a potent renal targeting drug carrier. Approximately 82% of the dose was accumulated in the kidney at 3 h after i.v. injection of 111 In-labeled Ser-PAMAM in mice, while i.v. injection of 111 In-labeled unmodified PAMAM, L-threonine modified PAMAM, and L-tyrosine modified PAMAM resulted in kidney accumulations of 28%, 35%, and 31%, respectively. Single-photon emission computed tomography/computed tomography (SPECT/ CT) images also indicated that 111 In-labeled Ser-PAMAM specifically accumulated in the kidneys. An intrakidney distribution study showed that fluorescein isothiocyanate-labeled Ser-PAMAM accumulated predominantly in renal proximal tubules. Results of a cellular uptake study of Ser-PAMAM in LLC-PK1 cells in the presence of inhibitors [genistein, 5-(N-ethyl-N-isopropyl)amiloride, and lysozyme] revealed that caveolae-mediated endocytosis, micropinocytosis, and megalin were associated with the renal accumulation of Ser-PAMAM. The efficient renal distribution and angiotensinconverting enzyme (ACE) inhibition effect of captopril (CAP), an ACE inhibitor, was observed after i.v. injection of the Ser-PAMAM-CAP conjugate. These findings indicate that Ser-PAMAM is a promising renal targeting drug carrier for the treatment of kidney diseases. Thus, the results of this study demonstrate efficient renal targeting of a drug carrier via Ser modification.drug delivery | renal targeting | L-serine | dendrimer

BackgroundPatient 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.MethodsNineteen 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.ResultsIn 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.ConclusionsThis 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.

Although single-photon-emitting radiotracers have long been the standard for renal functional molecular imaging, recent years have seen the development of positron emission tomography (PET) agents for this application. We provide an overview of renal radionuclide PET radiotracers, in particular focusing on novel 18 F-labelled and 68 Ga-labelled agents. Several reported PET imaging probes allow assessment of glomerular filtration rate, such as [ 68 Ga]ethylenediaminetetraacetic acid ([ 68 Ga]EDTA), [ 68 Ga]IRDye800-tilmanocept and 2-deoxy-2-[ 18 F]fluorosorbitol ([ 18 F]FDS)). The diagnostic performance of [ 68 Ga]EDTA has already been demonstrated in a clinical trial. [ 68 Ga]IRDye800-tilmanocept shows receptor-mediated binding to glomerular mesangial cells, which in turn may allow the monitoring of progression of diabetic nephropathy. [ 18 F]FDS shows excellent kidney extraction and excretion in rats and, as has been shown in the first study in humans. Further, due to its simple one-step radiosynthesis via the most frequently used PET radiotracer 2-deoxy-2-[ 18 F]fluoro- d -glucose, [ 18 F]FDS could be available at nearly every PET centre. A new PET radiotracer has also been introduced for the effective assessment of plasma flow in the kidneys: Re(CO) 3 - N -([ 18 F]fluoroethyl)iminodiacetic acid (Re(CO) 3 ([ 18 F]FEDA)). This compound demonstrates similar pharmacokinetic properties to its 99m Tc-labelled analogue [ 99m Tc](CO) 3 (FEDA). Thus, if there is a shortage of molybdenum-99, Re(CO) 3 ([ 18 F]FEDA would allow direct comparison with previous studies with 99m Tc. The PET radiotracers for renal imaging reviewed here allow thorough evaluation of kidney function, with the tremendous advantage of precise anatomical coregistration with simultaneously acquired CT images and rapid three-dimensional imaging capability.