[Achievement and Philosophy of Studies on SPECT Reconstruction Algorithms].

The purpose of this article is to introduce achievement and philosophy on studies of SPECT reconstruction algorithms which Dr. Eiichi Tanaka dedicated himself to carrying out. The method that Dr. Tanaka suggested first (in 1974) was to reconstruct analytically a section image from the projection data convoluted the correction functions. The correction functions were optimized to yield a maximum 'signal-to-noise ratio'. In 1983 and 1984, two image reconstruction algorithms, WBP and RPC were suggested assuming a uniform attenuation in the object. Dr. Tanaka understood intuitively that these methods had few noise and distortions in reconstructed images. WBP was an approximate solution, but three type analytically methods were reported by Tretiak O, et al., Bellini S, et al., and Inoyue T, et al. In 1995, Metz CE, et al. and Kudo H, et al. succeeded independently each other in finishing a general theory of the analytic absorption Radon Conversion by using parameter "n". The relations among the above three analytically methods and WBP were explained, beautifully. The important thing in the study is a flexible idea such as catching a problem as the issue of black box or reverse and the result to be concise and elegant.

A random forest algorithm-based approach to capture latent decision variables and their cutoff values.

Although reference intervals (RIs) and clinical decision limits (CDLs) are vital laboratory information for supporting the interpretation of numerical clinical pathology results, there is evidence that RIs and CDLs vary in certain contexts as well as other evidence that RIs and CDLs are flawed. We propose a random forest algorithm-based exploration methodology by using phenotype transformation of independent variables in relation to dependent variables to capture latent decision variables and their cutoff values. We denote certain CDLs within the RIs estimated by an indirect method that affect some diagnostics or outcomes in the context of specific patients' conditions as latent CDLs. We then apply the proposed methodology to clinical laboratory data regarding bodily fluids, such as blood, urine at the admission of patients for the exploration of latent CDLs of hospital length of stay (HLOS) for each patients' condition identified by diseases of patients who undergoing surgeries. From the exploration results, we found that free Thyroxine (T4) above five unique cutoff values: 1.16 ng/dL, 1.19 ng/dL, 1.2 ng/dL, 1.23 ng/dL and 1.25 ng/dL for tachyarrhythmia predicted longer HLOS, though these cutoff values fall within the estimated RIs as well as the hospital-determined RIs. In addition to the evidence that higher free Thyroxine (T4) levels within the RIs have an association with the corresponding disease, on the whole, the cutoff values except 1.16 ng/dL tended to affect long HLOS with the significant differences. The cutoff values could be taken up for discussion among clinical experts whether it is meaningful to alert the risk of patients' conditions and the long HLOS at the admission of patients. If clinical experts appreciate its meaningfulness in clinical practice, the alerts could be embedded in electronic medical records for handling those risks at the admission of patients.

Electronic teaching materials for inter-professional education in a college of medical professionals.

In order to promote the utilization of digital clinical information among medical professionals, an education program and electronic teaching materials involving fictitious model patients were developed for students in a health and welfare college. The purposes of this program were for students to learn the role of each medical professional and to understand the medical records written by each medical staff member in interdisciplinary medicine (a collaborative approach to medicine). The materials for fictitious patients, including medical records, study results, medical images and the associated documents, were stored in a database on a virtual private network. The electronic medical records were easily modified according to the specialty of the students in each class. Fictional medical records of patients with lacunar infarction, fracture of the distal radius, fracture of the femur, diabetes mellitus and breast cancer were generated and evaluated in inter-professional education classes.

Development of electronic progress tables for multidisciplinary medical education in a university.

In the education of medical professionals, imitation medical records and associated documents were developed as electronic teaching materials for students in order to teach collaboration among medical professionals such as nurses, therapists and medical social workers. The roles of each medical professional and the flow of clinical practice were taught using progress tables, including medical treatment, clinical examination, and the contents of care, so that the contents of medical examination were understood based on a time series. Students' understanding of the flow of medical practice was evaluated based on the amount of description in the table before and after explanation of the important points of the clinical process concerning each medical professional. The comments of students who received the lessons suggested that this approach was useful for understanding actual clinical practice and how to utilize a progress table and to prepare information.

Quantitative analyses of [¹¹C]Ro15-4513 binding to subunits of GABAA/benzodiazepine receptor in the living human brain.

BACKGROUND: Gamma-aminobutyric acid (GABA)A/benzodiazepine (BZ) receptor chloride channel consists of several subunits. The diversity of the α subunits results in the various ligand selectivity and functionally different properties of the GABAA/BZ receptor. Although [¹¹C] Ro15-4513 is reported to be a radioligand that has relatively high affinity for α5 subunit-containing GABAA/BZ receptor, it remained to be evaluated fully. AIM: The aim of this study was to evaluate the quantitative analyses of [¹¹C]Ro15-4513 in the living human brain. METHODS: Positron emission tomography examinations were performed in eight healthy male volunteers after intravenous injection of [¹¹C]Ro15-4513. Kinetic analysis of data was performed with the two-compartment and three-compartment models using arterial input function. Linear graphical analysis and the simplified reference tissue model analysis (SRTM) were also performed using pons as a reference region. In a simulation study, the effects of noise to the estimation of binding potentials were evaluated. RESULTS: The accumulation of [¹¹C]Ro15-4513 in the limbic system was relatively higher than in other cortex. The bindings were well described by the three-compartment model in the regions with specific binding. Binding potentials obtained from the graphical method and SRTM correlated well with those obtained from the three-compartment model. In the simulation study, estimated parameters from SRTM were less affected by noise compared with those from the graphical method. CONCLUSION: The reference tissue methods using pons as a reference region can be used for quantitative analysis of [¹¹C]Ro15-4513 binding. SRTM seemed less susceptible to noise than does graphical analysis.

A statistical clustering approach to visualizing the relationship between early and delayed images in whole-body FDG-PET.

We propose a new method for diagnostic assistance in oncology, [fluorine-18]-2-fluoro-2-deoxy-D: -glucose (FDG)-positron emission tomography (PET). Early and delayed scans were performed on 10 patients with lung cancer by use of an ECAT EXACT 47 PET scanner, and standardized-uptake-value (SUV) images were created. Three segmentation (S1, S2, and S3) maps were created from the early and delayed SUV images according to various thresholds (SUV(threshold) = 2.0, 2.5, and 3.0) based on the early image and the percentage change defined as (SUV(delayed) - SUV(early)) x 100/SUV(early). Voxels that had larger voxel values in their early images than the SUV(threshold) were clustered into three classes: S1 if the percentage change was larger than 10, S2 if the percentage change was between 0 and 10, and S3 if the percentage change was negative. The S1 segments showed malignant lesions clearly; however, the S2 segments showed an SUV that had decreased from the S1 areas due to the partial volume effect or misalignment between the early and delayed scans. The S3 areas showed benignity or physiologic accumulation. The segmented images, S1, S2, and S3, were useful for clinical diagnosis with dual-phase FDG-PET scans and offer an easy way of exploring the longitudinal alteration in the SUV.

Nurses' views on the use, quality and user satisfaction with electronic medical records: questionnaire development.

AIM: This paper is a report of the development of an instrument to measure nurses' views on the use, quality and user satisfaction with electronic medical records systems. BACKGROUND: Use of electronic medical records systems in hospitals is steadily increasing, yet no validated instruments have assessed the effectiveness of these systems from the viewpoint of nurses. METHOD: Items were designed following a literature review based on three main constructs: use, quality and user satisfaction with electronic medical records. Reliability and validity were examined based on responses from 1,666 nurses from 42 hospitals in Japan in February 2006. Exploratory factor analysis was conducted to determine the degree to which each item within a construct was associated. The reliability of each resultant factor was computed using Cronbach's alpha coefficient. Content validity was addressed by basing the items on previous surveys and review of the instrument by a panel of nurses experienced in nursing informatics. Construct validity was examined through factor analysis and correlational analyses. FINDINGS: Extent of 'use' of electronic medical records resulted into three factors with good factor loadings, but only two had acceptable reliability. 'Quality' of electronic medical records had two factors with good factor loadings and reliability. 'User satisfaction' with electronic medical records had three factors, but only one had acceptable reliability. 'Use' and 'quality' constructs were positively correlated with 'user satisfaction'. CONCLUSION: The final instrument incorporates 34 items from the original 44-item pool. Initial validity results were positive and therefore the instrument can be used in evaluating electronic medical records in hospitals.

Quantitative analysis for estimating binding potential of the peripheral benzodiazepine receptor with [(11)C]DAA1106.

[(11)C]DAA1106 is a potent and selective ligand for the peripheral benzodiazepine receptor (PBR) with high affinity. It has been reported that the density of PBR is related to brain damage, so a reliable tracer method for the evaluation of PBR would be of use. We evaluated a quantification method of [(11)C]DAA1106 binding in simulated data and human brain data. In the simulation study, the reliability of parameters estimated from the nonlinear least-squares (NLS) method, graphical analysis (GA), and multilinear analysis (MA) was evaluated. In GA, variation of the estimated distribution volume (DV) was small. However, DV was underestimated as noise increased. In MA, bias was smaller, and variation of the estimated DV was larger than in GA. In NLS, although variation was larger than in GA, it was small enough in regions of interest analysis, and not only DV but also binding potential (BP), determined from the k(3)/k(4) without any constraint, could be estimated. The variation of BP estimated with NLS became larger as k(3) or k(4) became smaller. In human studies with normal volunteers, regions of interest were drawn on several brain regions, BP was calculated by NLS, and DV was also estimated by NLS, GA, and MA. As a result, DVs estimated with each method were well correlated. However, there was no correlation between BP with NLS and DV with NLS, GA, and MA, because of the variation of K(1)/k(2) between individuals. In conclusion, BP is estimated most reliably by NLS with the two-tissue compartment model.

Quantitative in vivo measurement of central benzodiazepine receptors in the brain of cats by use of positron-emission tomography and [11C]flumazenil.

OBJECTIVE: To map central benzodiazepine receptors (BZRs) in the brain of cats by use of positron-emission tomography (PET) and [11C]flumazenil. ANIMALS: 6 male cats that weighed between 2.0 and 3.6 kg. PROCEDURE: Brain images obtained by PET evaluation of [11C]flumazenil were superimposed on T2-weighted magnetic-resonance imaging (MRI) scans of the same cats. Detailed anatomic regions, such as the cerebral cortex, striatum, thalamus, midbrain, and cerebellum, on the PET images were evident by PET-MRI registration. Regional binding of [11C]flumazenil to BZRs was quantitatively measured by use of a model with 2 tissue compartments and 4 variables. RESULTS: The highest value for distribution volume was observed in the cerebral cortex, and the lowest value was found in the midbrain of cats. CONCLUSIONS AND CLINICAL RELEVANCE: Binding of [11C]flumazenil to BZRs in the brain of cats can be quantitatively measured by use of PET with the aid of PET-MRI registration. It is difficult to diagnose changes in these neuroreceptors within the field of current veterinary science. In the future, PET should prove useful for investigating and diagnosing brain disorders in animals in clinical settings.

Increased regional cerebral blood flow but normal distribution of GABAA receptor in the visual cortex of subjects with early-onset blindness.

Before the completion of visual development, visual deprivation impairs synaptic elimination in the visual cortex. The purpose of this study was to determine whether the distribution of central benzodiazepine receptor (BZR) is also altered in the visual cortex in subjects with early-onset blindness. Positron emission tomography was carried out with [(15)O]water and [(11)C]flumazenil on six blind subjects and seven sighted controls at rest. We found that the CBF was significantly higher in the visual cortex for the early-onset blind subjects than for the sighted control subjects. However, there was no significant difference in the BZR distribution in the visual cortex for the subject with early-onset blindness than for the sighted control subjects. These results demonstrated that early visual deprivation does not affect the distribution of GABA(A) receptors in the visual cortex with the sensitivity of our measurements. Synaptic elimination may be independent of visual experience in the GABAergic system of the human visual cortex during visual development.

Template-based method for multiple volumes of interest of human brain PET images.

Specific region-based analysis for the quantification of brain imaging is very time-consuming work and subject to errors in both accuracy and reproducibility. In this study, we assessed a two-step template-based method for defining volumes of interest (VOIs). The first step was the spatial transformation of the VOI template from a model MRI to an individual MRI with SPM99. The second step was to refine the transformed VOI to the individual gray matter of MRI using the intensity characteristics of this image with our developed software running on a PC type of computer. The reliability of the values of the final refined VOIs was investigated by comparing them to those of manually drawn VOIs. The template-based method was found to be both accurate and robust and can be used as a reliable alternative for the manual determination of VOIs.

Positron emission tomography and ex vivo and in vitro autoradiography studies on dopamine D2-like receptor degeneration in the quinolinic acid-lesioned rat striatum: comparison of [11C]raclopride, [11C]nemonapride and [11C]N-methylspiperone.

With [11C]raclopride,[11C]nemonapride and [11C]N-methylspiperone, degeneration of dopamine D2-like receptors in the unilaterally quinolinic acid-lesioned rats was evaluated by positron emission tomography (PET) and ex vivo and in vitro autoradiography. PET showed a decreased uptake of [11C]raclopride in the lesioned striatum, but an increased uptake of [11C]nemonapride and [11C]N-methylspiperone despite a decreased binding in vitro. Ex vivo autoradiography showed an increased accumulation of the three ligands in the cortical region overlying the injured striatum, probably enlarging PET signals. PET has the limited potential for evaluating the receptor degeneration in the present animal model.

Quantitative analysis for estimating binding potential of the brain serotonin transporter with [11 C]McN5652.

SUMMARY: [11C](+)McN5652 is a selective serotonin reuptake inhibitor with subnanomolar potency for the serotonin transporter, and is currently being used for positron emission tomography studies. However, quantification of the regional [11C](+)McN5652 binding potential in vivo is a controversial issue because of its complex characteristics. The authors examined the regional differences in nonspecific binding and proposed simple methods for estimating the binding potential of [11C](+)McN5652. The regional difference in nonspecific binding was evaluated by the activity ratio of the thalamus compared with the cerebellum for inactive-isomer [11C](-)McN5652 and [11C](+)McN5652 saturation studies. The distribution volume of the thalamus was approximately 1.16 times larger than that of the cerebellum. The thalamus-to-cerebellum distribution volume ratio was estimated by nonlinear least square and graphical methods, with and without arterial input function. The graphical method with k2; without blood sampling was practical and most applicable for estimation of the distribution volume ratio because this method is more stable than the nonlinear least square method in the simulation study. Binding potential estimated with the distribution volume ratio of [11C](+)McN5652 and the correction with distribution volume ratio of [11C](-)McN5652 represent the most reliable parameters for the assessment of serotonin transporter binding.

Mapping adenosine A(1) receptors in the cat brain by positron emission tomography with [(11)C]MPDX.

We evaluated the potential of [(11)C]MPDX as a radioligand for mapping adenosine A(1) receptors in comparison with previously proposed [(11)C]KF15372 in cat brain by PET. Two tracers showed the same brain distribution. Brain uptake of [(11)C]MPDX (Ki = 4.2 nM) was much higher and washed out faster than that of [(11)C]KF15372 (Ki = 3.0 nM), and was blocked by carrier-loading or displaced with an A(1) antagonist. The regional A(1) receptor distribution evaluated with kinetic analysis is consistent with that previously measured in vitro. [(11)C]MPDX PET has a potential for mapping adenosine A(1) receptors in brain.

Fast determination method of cerebral metabolic rate images of glucose using dynamic PET data.

Measurement of the rate constant parameters of the tracer 18F-FDG, used with positron emission tomography (PET) to determine the cerebral metabolic rate of glucose (CMRGlc), can provide a clear understanding of the physiological processes in the human brain. At present, the methods that are widely used to obtain CMRGlc, such as nonlinear least squares (NLS), first require the reconstruction of a time sequence of images. The reconstruction of these images requires a large amount of computation, especially in 3D Depth-of Interaction PET (DOI-PET), and the nonlinear based methods also require a large amount of computation. In this paper, we propose a fast parametric image reconstruction method for 18F-FDG dynamic PET studies. In our method a deconvolving process is first employed on the time sequential projection data to remove the effect of the measured plasma time activity. The deconvolved terms are integrated over three different time intervals and the parameters for determining CMRGlc can be obtained analytically. Our method requires only three reconstructing processes and reduces the computational demand to estimate CMRGlc. The algorithm performance is evaluated using a digital phantom and a clinical data set and the results show that the proposed method produces images with the same or better quality as the images from the NLS method, with much less computation compared to the NLS method.

Adenosine A2A receptor imaging with [11C]KF18446 PET in the rat brain after quinolinic acid lesion: comparison with the dopamine receptor imaging.

We proposed [11C]KF18446 as a selective radioligand for mapping the adenosine A2A receptors being highly enriched in the striatum by positron emission tomography (PET). In the present study, we investigated whether [11C]KF18446 PET can detect the change in the striatal adenosine A2A receptors in the rat after unilateral injection of an excitotoxin quinolinic acid into the striatum, a Huntington's disease model, to demonstrate the usefulness of [11C]KF18446. The extent of the striatal lesion was identified based on MRI, to which the PET was co-registered. The binding potential of [11C]KF18446 significantly decreased in the quinolinic acid-lesioned striatum. The decrease was comparable to the decrease in the potential of [11C]raclopride binding to dopamine D2 receptors in the lesioned striatum, but seemed to be larger than the decrease in the potential of [11C]SCH 23390 binding to dopamine D1 receptors. Ex vivo and in vitro autoradiography validated the PET signals. We concluded that [11C]KF18446 PET can detect change in the adenosine A2A receptors in the rat model, and will provide a new diagnostic tool for characterizing post-synaptic striatopallidal neurons in the stratum.