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A new method has been developed for diffusible tracers, to quantify CBF at rest and after pharmacological stress from a single session of dynamic scans with dual bolus administration of a radiotracer. The calculation process consisted of three steps, including the procedures of incorporating background radioactivity contaminated from the previous scan. Feasibility of this approach was tested on clinical SPECT studies on 16 subjects. Two sequential SPECT scans, 30 min apart, were carried out on each subject, after each of two split-dose administrations of 111 MBq IMP. Of these, 11 subjects received acetazolamide at 10 min before the second IMP injection. Additional PET scans were also carried out on 6 subjects on a separate day, at rest and after acetazolamide administration. The other 5 subjects were scanned only at rest during the whole study period. Quantitative CBF obtained by this method was in a good agreement with those determined with PET (y(ml/100 g/min)=1.07x(ml/100 g/min)-1.14, r=0.94). Vasareactivity was approximately 40% over the whole cerebral area on healthy controls, which was consistent with a literature value. Reproducibility of CBF determined in the rest-rest study was 1.5+/-5.7%. Noise enhancement of CBF images, particularly the second CBF, was reduced, providing reasonable image quality. Repeat assessment of quantitative CBF from a single session of scans with split-dose IMP is accurate, and may be applied to clinical research for assessing vascular reactivity in patients with chronic cerebral vascular disease.

Objective: We compared the diagnostic accuracy achieved by a human observer (nuclear medicine physician) and a channelized Hotelling (CH) observer on the basis of receiver-operating characteristics (ROC) curve for the differential diagnosis of Alzheimer's disease (AD) from SPECT images., Methods: The I-123-IMP brain perfusion SPECT images of 42 subjects (21 AD patients and 21 healthy controls) were used for an interpretation study and those of 10 healthy subjects were for a normal database. SPECT images were processed into four types: original SPECT images, three-dimensional stereotactic surface projection (3DSSP) images derived from them, Z-scores of SPECT images, and Z-scores of 3DSSP images. Five nuclear medicine physicians evaluated the test dataset sequentially as to whether the presented images were those of AD patients, which were rated using five categories of certainty: definitely, possibly, equivocally, possibly not, and definitely not. The test statistics (lambda) of the dataset generated by the CH observer were rated for ROC analysis. The areas under the ROC curves (Az) for the four image types interpreted by the human and CH observers were estimated and compared., Results: Among the four image types, the best performance based on Az obtained by both the CH and human observers was observed for the Z-score of 3DSSP images, and the lowest was for the original SPECT images., Conclusions: The performance of the CH observer was similar to that of the human observers, and both were dependent on the image type. This indicates that the CH observer may predict human performance in discriminating Alzheimer's dementia and can be useful for comparing and optimizing image processing methods of brain perfusion SPECT without human observers.

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.

Background and Objectives: Statistical reconstruction methods allow resolution recovery in tomographic reconstruction. Even though resolution recovery has the potential to improve overall image quality, pinhole SPECT images are still often reconstructed using simplified models of the acquisition geometry in order to reduce reconstruction time. This paper investigates the benefits of two resolution recovery methods, multi-ray and point-spread function based, in pinhole SPECT by comparing them to uncorrected reconstruction., Methods: Resolution recovery was incorporated into ordered subsets expectation maximization reconstruction algorithm. The first of the correction methods used a simple but very fast multiple projection ray approach, whereas the second, much slower, method modelled the acquisition geometry more accurately using the analytical point-spread function of the pinhole collimator. Line source, Jaszczak and contrast phantom studies were performed and used for comparison., Results: Resolution recovery improved resolution, contrast and visual quality of the images when compared to reconstructions without it. The method based on the point-spread function performed slightly better, but was almost 50 times slower than the much simpler multi-ray approach., Conclusion: The multiple projection ray approach is a promising method for very fast and easy resolution recovery in pinhole SPECT. It has a profound effect on image quality and can markedly improve the resolution-sensitivity trade-off.

Objectives: Pinhole SPECT which permits in vivo high resolution 3D imaging of physiological functions in small animals facilitates objective assessment of pharmaceutical development and regenerative therapy in pre-clinical trials. For handiness and mobility, the miniature size of the SPECT system is useful. We developed a small animal SPECT system based on a compact high-resolution gamma camera fitted to a pinhole collimator and an object-rotating unit. This study was aimed at evaluating the basic performance of the detection system and the feasibility of small animal SPECT imaging., Methods: The gamma camera consists of a 22 x 22 pixellated scintillator array of 1.8 mm x 1.8 mm x 5 mm NaI(Tl crystals with 0.2-mm gap between the crystals coupled to a 2" flat panel position-sensitive photomultiplier tube (Hamamatsu H8500) with 64 channels. The active imaging region of the camera was 43.8 mm x 43.8 mm. Data acquisition is controlled by a personal computer (Microsoft Windows) through the camera controller. Projection data over 360 degrees for SPECT images are obtained by synchronizing with the rotating unit. The knife-edge pinhole collimators made of tungsten are attached on the camera and have 0.5-mm and 1.0-mm apertures. The basic performance of the detection system was evaluated with 99mTc and 201Tl solutions. Energy resolution, system spatial resolution and linearity of count rate were measured. Rat myocardial perfusion SPECT scans were sequentially performed following intravenous injection of 201TlCl. Projection data were reconstructed using a previously validated pinhole 3D-OSEM method., Results: The energy resolution at 140 keV was 14.8% using a point source. The system spatial resolutions were 2.8-mm FWHM and 2.5-mm FWHM for 99mTc and 201Tl line sources, respectively, at 30-mm source distance (magnification factor of 1.3) using a 1.0-mm pinhole. The linearity between the activity and count rate was good up to 10 kcps. In a rat study, the left ventricular walls were clearly visible in all scans., Conclusions: We developed a compact SPECT system using compact gamma camera for small animals and evaluated basic physical performances. The present system may be of use for quantitation of biological functions such as myocardial blood flow in small animals.

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.

Purpose: An image-based scatter correction (IBSC) method was developed to convert scatter-uncorrected into scatter-corrected SPECT images. The purpose of this study was to validate this method by means of phantom simulations and human studies with 99mTc-labeled tracers, based on comparison with the conventional triple energy window (TEW) method., Methods: The IBSC method corrects scatter on the reconstructed image I(mub)AC with Chang's attenuation correction factor. The scatter component image is estimated by convolving I(mub)AC with a scatter function followed by multiplication with an image-based scatter fraction function. The IBSC method was evaluated with Monte Carlo simulations and 99mTc-ethyl cysteinate dimer SPECT human brain perfusion studies obtained from five volunteers. The image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were compared., Results: Using data obtained from the simulations, the image counts and contrast of the scatter-corrected images obtained by the IBSC and TEW methods were found to be nearly identical for both gray and white matter. In human brain images, no significant differences in image contrast were observed between the IBSC and TEW methods., Conclusion: The IBSC method is a simple scatter correction technique feasible for use in clinical routine.

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.

Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO(2)) may be quantified using positron emission tomography (PET) with (15)O-tracers, but the conventional three-step technique requires a relatively long study period, attributed to the need for separate acquisition for each of (15)O(2), H(2)(15)O, and C(15)O tracers, which makes the multiple measurements at different physiologic conditions difficult. In this study, we present a novel, faster technique that provides a pixel-by-pixel calculation of CBF and CMRO(2) from a single PET acquisition with a sequential administration of (15)O(2) and H(2)(15)O. Experiments were performed on six anesthetized monkeys to validate this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO(2) obtained by the present technique at rest were not significantly different from those obtained with three-step method. The global OEF (gOEF) also agreed with that determined by simultaneous arterio-sinus blood sampling (gOEF(A-V)) for a physiologically wide range when changing the arterial PaCO(2) (gOEF=1.03gOEF(A-V)+0.01, P<0.001). The regional values, as well as the image quality were identical between the present technique and three-step method for CBF, OEF, and CMRO(2). In addition, a simulation study showed that error sensitivity of the present technique to delay or dispersion of the input function, and the error in the partition coefficient was equivalent to that observed for three-step method. Error sensitivity to cerebral blood volume (CBV) was also identical to that in the three-step and reasonably small, suggesting that a single CBV assessment is sufficient for repeated measures of CBF/CMRO(2). These results show that this fast technique has an ability for accurate assessment of CBF/CMRO(2) and also allows multiple assessment at different physiologic conditions.

Recently, lactate has been receiving great attention as an energy substrate in the brain. In this study, the role of lactate was evaluated by "bioradiography" system with 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), which is a positron emitting radiotracer for glucose uptake quantification. "Bioradiography" is the dynamic living tissue slice imaging system for positron-emitter labeled compounds. We investigated the brain energy metabolism under resting state and neural activated conditions induced by KCl addition. The monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), had no effect on [(18)F]FDG uptake rate in rat brain slices before KCl addition. On the other hand, addition of 4-CIN induced larger [(18)F]FDG uptake rates under the activated condition in comparison with the control condition. Because neurons cannot utilize lactate under the 4-CIN loaded conditions, this indicates that activated neurons consume lactate as an energy substrate. The lactate concentration in the incubation medium was increased with KCl treatment in both groups and the extent was slightly greater in 4-CIN group. These results suggested that: (1) the brain mainly uses glucose, not lactate, as an energy substrate in resting state; (2) when neuron is stimulated, excess amounts of lactate might be produced in astrocytes and the lactate is mobilized as an energy substrate.

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.

Central neuropathic pain (CNP) is pain resulting from damage to the central nervous system. Up till now, it has not been possible to identify a common lesion or pharmacological deficit in these patients. This preliminary study in a group of patients with CNP with predominantly post-stroke pain, demonstrates that there is significantly less opioid receptor binding in a number of cortical and sub-cortical structures that are mostly, but not exclusively, within the medial pain system in patients compared to age-matched pain-free controls. The reductions in opioid receptor binding within the medial system were observed mainly in the dorsolateral (Brodman area 10) and anterior cingulate (Brodman area 24 with some extension into area 23) and insula cortices and the thalamus. There were also reductions in the lateral pain system within the inferior parietal cortex (Brodman area 40). These changes in binding could not be accounted for by the cerebral lesions shown by CT or MRI, which were outside the areas of reduced binding and the human pain system. To our knowledge this is the first systematic demonstration of a reduction in opioid receptor-binding capacity in neurones within the human nociceptive system in patients with CNP. This may be a key common factor resulting in undamped nociceptor activity within some of the structures that are predominantly within the medial nociceptive system. If confirmed, these findings may explain why certain patients with CNP require high doses of synthetic opiates to achieve optimum analgesia. The findings also raise the possibility of new pharmacological approaches to treatment.

Pinhole single-photon emission computed tomography (SPECT) is able to provide information on the biodistribution of several radioligands in small laboratory animals, but has limitations associated with non-uniform spatial resolution or axial blurring. We have hypothesised that this blurring is due to incompleteness of the projection data acquired by a single circular pinhole orbit, and have evaluated a new strategy for accurate image reconstruction with better spatial resolution uniformity. A pinhole SPECT system using two circular orbits and a dedicated three-dimensional ordered subsets expectation maximisation (3D-OSEM) reconstruction method were developed. In this system, not the camera but the object rotates, and the two orbits are at 90 degrees and 45 degrees relative to the object's axis. This system satisfies Tuy's condition, and is thus able to provide complete data for 3D pinhole SPECT reconstruction within the whole field of view (FOV). To evaluate this system, a series of experiments was carried out using a multiple-disk phantom filled with 99mTc solution. The feasibility of the proposed method for small animal imaging was tested with a mouse bone study using 99mTc-hydroxymethylene diphosphonate. Feldkamp's filtered back-projection (FBP) method and the 3D-OSEM method were applied to these data sets, and the visual and statistical properties were examined. Axial blurring, which was still visible at the edge of the FOV even after applying the conventional 3D-OSEM instead of FBP for single-orbit data, was not visible after application of 3D-OSEM using two-orbit data. 3D-OSEM using two-orbit data dramatically reduced the resolution non-uniformity and statistical noise, and also demonstrated considerably better image quality in the mouse scan. This system may be of use in quantitative assessment of bio-physiological functions in small animals.

Unlabelled: The rupture of atherosclerotic plaques and the subsequent formation of thrombi are the main factors responsible for myocardial and cerebral infarctions. Thus, the detection of vulnerable plaques in atherosclerotic lesions is a desirable goal, and attempts to image these plaques with (18)F-FDG have been made. In the present study, the relationship between the accumulation of (18)F-FDG and the biologic characteristics of atherosclerotic lesions was investigated. Furthermore, PET imaging of vulnerable plaques was performed with an animal model of atherosclerosis, Watanabe heritable hyperlipidemic (WHHL) rabbits., Methods: WHHL (n = 11) and control (n = 3) rabbits were injected intravenously with (18)F-FDG, and the thoracic and abdominal aortas were removed 4 h after injection. The accumulated radioactivity was measured, and the number of macrophages and the intimal area were investigated by examination of stained sections. PET and CT images were also acquired at 210 min after injection of the radiotracer., Results: (18)F-FDG accumulated to a significantly higher level in the aortas of the WHHL rabbits (mean +/- SD differential uptake ratio [DUR], 1.47 +/- 0.90) than in those of the control rabbits (DUR, 0.44 +/- 0.15); DUR was calculated as (tissue activity/tissue weight)/(injected radiotracer activity/animal body weight), with activities given in becquerels and weights given in kilograms. (18)F-FDG uptake and the number of macrophages were strongly correlated in the atherosclerotic lesions of the WHHL rabbits (R = 0.81). In the PET analysis, intense (18)F-FDG radioactivity was detected in the aortas of the WHHL rabbits, whereas little radioactivity was seen in the control rabbits., Conclusion: The results suggest that macrophages are responsible for the accumulation of (18)F-FDG in atherosclerotic lesions. Because vulnerable plaques are rich in macrophages, (18)F-FDG imaging should be useful for the selective detection of such plaques.

Repetitive transcranial magnetic stimulation (rTMS) recently has been assessed as a noninvasive treatment modality for movement and psychiatric disorders, whereas the mechanism underlying the therapeutic effects is not fully understood. Studies in rodents showed lasting functional changes in some selected regions, such as limbic-associated structures, but unfocused brain stimulation did not clarify the regional effects. To address the topographical and temporal profiles of the effects on glucose metabolism in primate brain, we performed rTMS and repeated (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) before, during, and up to 16 days after rTMS in anesthetized cynomologous monkeys. We delivered a total of 2,000 pulses of 5 Hz-rTMS over the right precentral gyrus using a small-sized eight-figured coil that induced a localized electrical field. Voxel-based analysis in a standard space of the macaque brain showed statistically robust changes in FDG uptake: a decrease in the motor/premotor cortices and an increase in the limbic-associated areas involving the anterior/posterior cingulate, and orbitofrontal cortices. Interestingly, these uptake changes continued for at least 8 days and the magnitude of the lasting effects in the limbic-related areas was negatively correlated across subjects with those in the motor/premotor cortices. The results demonstrate that motor rTMS has a long-term lasting effect on motor-related regions and distant limbic-related areas via functional connections.

Prior studies with anthropomorphic phantoms and single, static in vivo brain images have demonstrated that scatter correction significantly improves the accuracy of regional quantitation of single-photon emission tomography (SPET) brain images. Since the regional distribution of activity changes following a bolus injection of a typical neuroreceptor ligand, we examined the effect of scatter correction on the compartmental modeling of serial dynamic images of striatal and extrastriatal dopamine D(2) receptors using [(123)I]epidepride. Eight healthy human subjects [age 30+/-8 (range 22-46) years] participated in a study with a bolus injection of 373+/-12 (354-389) MBq [(123)I]epidepride and data acquisition over a period of 14 h. A transmission scan was obtained in each study for attenuation and scatter correction. Distribution volumes were calculated by means of compartmental nonlinear least-squares analysis using metabolite-corrected arterial input function and brain data processed with scatter correction using narrow-beam geometry micro (SC) and without scatter correction using broad-beam micro (NoSC). Effects of SC were markedly different among brain regions. SC increased activities in the putamen and thalamus after 1-1.5 h while it decreased activity during the entire experiment in the temporal cortex and cerebellum. Compared with NoSC, SC significantly increased specific distribution volume in the putamen (58%, P=0.0001) and thalamus (23%, P=0.0297). Compared with NoSC, SC made regional distribution of the specific distribution volume closer to that of [(18)F]fallypride. It is concluded that SC is required for accurate quantification of distribution volumes of receptor ligands in SPET studies.

MRI (magnetic resonance imaging) with 129Xe has gained much attention as a diagnostic methodology because of its affinity for lipids and possible polarization. The quantitative estimation of net detectability and stability of hyperpolarized 129Xe in the dissolved phase in vivo is valuable to the development of clinical applications. The goal of this study was to develop a stable hyperpolarized 129Xe experimental 3T system to statistically analyze the dissolved-phase 129Xe signal in the rat lungs. The polarization of 129Xe with buffer gases at the optical pumping cell was measured under adiabatic fast passage against the temperature of an oven and laser absorption at the cell. The gases were insufflated into the lungs of Sprague-Dawley rats (n = 15, 400-550 g) through an endotracheal tube under spontaneous respiration. Frequency-selective spectroscopy was performed for the gas phase and dissolved phase. We analyzed the 129Xe signal in the dissolved phase to measure the chemical shift, T2*, delay and its ratio in a rat lungs on 3T. The polarizer was able to produce polarized gas (1.1+/-0.47%, 120 cm3) hundreds of times with the laser absorption ratio (25%) kept constant at the cell. The optimal buffer gas ratio of 25-50% rendered the maximum signal in the dissolved phase. Two dominant peaks of 211.8+/-0.9 and 201.1+/-0.6 ppm were observed with a delay of 0.4+/-0.9 and 0.9+/-1.0 s from the gas phase spectra. The ratios of their average signal to that of the gas phase were 5.6+/-5.2% and 4.4+/-4.7%, respectively. The T2* of the air space in the lungs was 2.5+/-0.5 ms, which was 3.8 times shorter than that in a syringe. We developed a hyperpolarized 129Xe experimental system using a 3T MRI scanner that yields sufficient volume and polarization and quantitatively analyzed the dissolved-phase 129Xe signal in the rat lungs.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been used as a treatment for neuropsychiatric disorders such as depression and Parkinson's disease (PD). Despite the growing interest in therapeutic application of rTMS, precise mechanisms of its action remain unknown. With respect to PD, activation of the mesostriatal dopaminergic pathway is likely to be a candidate mechanism underlying the therapeutic effects; however, modulating effects of rTMS over the primary motor cortex (M1) on the dopaminergic system have not been studied., Methods: We used [11C]raclopride positron emission tomography to measure changes of extracellular dopamine concentration after 5Hz rTMS over the M1 in eight anesthetized monkeys., Results: rTMS over the right M1 induced a reduction of [11C]raclopride binding potential (BP) in the bilateral ventral striatum, including the nucleus accumbens, and a significant increase of BP in the right putamen; no significant BP reduction was found in the dorsal striatum. These data indicate that rTMS over the motor cortex induces a release of endogenous dopamine in the ventral striatum., Conclusions: Our results suggest that therapeutic mechanisms of rTMS may be explained in part by an activation of the mesolimbic dopaminergic pathway, which plays critical roles in rewards, reinforcement, and incentive motivation.

The difference in tracer arrival times between the external radiation detector and the brain following administration of radioactivity (delay time) must be estimated correctly in order to quantitatively measure regional cerebral blood flow (rCBF) with positron emission tomography and [15O]H2O by autoradiographic method. Instead of intervenous injection of [15O]H2O, bolus inhalation of [15O]CO2 gas is sometimes used to simplify the measurement of rCBF. In the case of [15O]CO2, radioactive gas in mask and nasal cavity contributes large artifact on the sinogram data and it is difficult to estimate delay time from the sinogram data. In this paper, we proposed a new method to estimate the delay time using the sinogram data and the attenuation map (attenuation weighted sinogram method). In the present method, the attenuation map was used to eliminate the effect of the gas outside the brain region from the sinogram data. For the validation of the present method, PET data with [15O]CO2 (n = 10) were analyzed. Three methods, namely the image method, the sinogram method and the attenuation weighted sinogram method were used to estimate the delay time. The estimated delay times and calculated rCBF images by three methods were compared. Due to the radioactivity outside of the brain, the sinogram method significantly overestimated the delay time and thus underestimated the rCBF value compared with the image base method. On the other hand, there were good agreements between the delay times estimated by the attenuation weighted sinogram method and the image method. The present method can eliminate the effect of the radioactivity outside of the brain on the sinogram data and estimate the delay time accurately and fast enough for clinical use.

The coupling of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) during physiologic and pathophysiologic conditions remains the subject of debate. In the present study, we have developed a theoretical model for oxygen delivery and metabolism, which describes the diffusion of oxygen at the capillary-tissue interface and the nonlinear nature of hemoglobin (Hb) affinity to oxygen, allowing a variation in simple-capillary oxygen diffusibility, termed "effective oxygen diffusibility (EOD)." The model was used to simulate the relationship between CBF and CMRO2, as well as oxygen extraction fraction (OEF), when various pathophysiologic conditions were assumed involving functional activation, ischemia, hypoxia, anemia, or hypo- and hyper-capnic CBF variations. The simulations revealed that, to maintain CMRO2 constant, a variation in CBF and Hb required active change in EOD. In contrast, unless the EOD change took place, the brain allowed small but significant nonlinear change in CMRO2 directly dependent upon oxygen delivery. Application of the present model to quantitative neuroimaging of CBF and CMRO2 enables us to evaluate the biologic response at capillary level other than Hb- and flow-dependent properties of oxygen transport and may give us another insight regarding the physiologic control of oxygen delivery in the human brain.

The equivalent mixture of cis-3-hexenol and trans-2-hexenal (hexenol/hexenal), 'green odor', is known to have a healing effect on the psychological damage caused by stress. Behavioral studies in humans and monkeys have revealed that hexenol/hexenal prevents the prolongation of reaction time caused by fatigue. In the present study, we investigated which brain regions are activated by the odor of hexenol/hexenal using positron emission tomography with alert monkeys. Regional cerebral blood flow (rCBF) in the prepyriform area (the primary olfactory cortex) was commonly increased by the passive application of odor: acetic acid, isoamylacetate or hexenol/hexenal. We observed rCBF increases in the orbitofrontal cortex (the secondary olfactory cortex) by these olfactory stimuli in two of three monkeys, and found no predominance of laterality of the activated hemisphere. Furthermore, rCBF increase in the cerebellum was observed in two of three monkeys, and the odor of acetic acid increased rCBF in the substantia innominata in all monkeys. In addition to these olfactory related regions, the anterior cingulate gyrus was activated by the odor of hexenol/hexenal. These findings suggest that the increase of rCBF in the anterior cingulate gyrus by the odor of hexenol/hexenal may contribute the healing effects of this mixture observed in the monkey.

Pinhole collimation can be used to improve spatial resolution in SPET. However, the resolution improvement is achieved at the cost of reduced sensitivity, which leads to projection images with poor statistics. Images reconstructed from these projections using the maximum likelihood expectation maximization (ML-EM) algorithms, which have been used to reduce the artefacts generated by the filtered backprojection (FBP) based reconstruction, suffer from noise/bias trade-off: noise contaminates the images at high iteration numbers, whereas early abortion of the algorithm produces images that are excessively smooth and biased towards the initial estimate of the algorithm. To limit the noise accumulation we propose the use of the pinhole median root prior (PH-MRP) reconstruction algorithm. MRP is a Bayesian reconstruction method that has already been used in PET imaging and shown to possess good noise reduction and edge preservation properties. In this study the PH-MRP algorithm was accelerated with the ordered subsets (OS) procedure and compared to the FBP, OS-EM and conventional Bayesian reconstruction methods in terms of noise reduction, quantitative accuracy, edge preservation and visual quality. The results showed that the accelerated PH-MRP algorithm was very robust. It provided visually pleasing images with lower noise level than the FBP or OS-EM and with smaller bias and sharper edges than the conventional Bayesian methods.

In quantitative pinhole SPECT, photon penetration through the collimator edges (penetration), and photon scattering by the object (object scatter) and collimator (collimator scatter) have not been investigated rigorously. Monte Carlo simulation was used to evaluate these three physical processes for different tungsten knife-edge pinhole collimators using uniform, hotspot and donut phantoms filled with 201Tl, 99mTc, 123I and 131I solutions. For the hotspot phantom, the penetration levels with respect to total counts for a 1 mm pinhole aperture were 78%, 28% and 23% for 131I, 123I and 99mTc, respectively. For a 2 mm aperture, these values were 65% for 131I, 16% for 123I and 12% for 99mTc. For all pinholes, 201Tl penetration was less than 4%. The evaluated scatter (from object and collimator) with a hotspot phantom for the 1 mm pinhole was 24%, 16%, 18% and 13% for 201Tl, 99mTc, 123I and 131I, respectively. Summation of the object and collimator scatter for the uniform phantom was approximately 20% higher than that for the hotspot phantom. Significant counts due to penetration and object and collimator scatter in the reconstructed image were observed inside the core of the donut phantom. The collimator scatter can be neglected for all isotopes used in this study except for 131I. Object scatter correction for all radionuclides used in this study is necessary and correction for the penetration contribution is necessary for all radionuclides but 201Tl.

Unlabelled: Correction of scatter and attenuation is essential for quantitative SPECT. In this work, we evaluated the accuracy gained from a method of transmission-dependent convolution subtraction (TDCS) in the quantitation of activity that is highly concentrated in the striatum (STR)., Methods: SPECT data were acquired from an (123)I-containing phantom with a constant activity in the STR but differing background (BKG) activities, so as to simulate various STR/BKG ratios (19.7:1, 9.7:1, 4.8:1, 1.9:1, and 1:1). In a study of healthy humans (n = 6), a transmission scan followed by an emission scan was performed 24 h after injection of (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane ((123)I-beta-CIT). All SPECT data was reconstructed with ordered-subset expectation maximization. TDCS was applied for scatter correction. Values of activity in the STR and occipital lobe (for BKG) were used to calculate binding potential V(3)" (= [STR - BKG]/BKG). The effect of SPECT collimator dependency on scatter correction was also evaluated for 6 collimators from 3 different SPECT cameras in the phantom experiment., Results: Scatter correction in the phantom experiment increased the measured values of STR activity (36.2%), resulting in a substantial increase in V(3)" (66.1%). Scatter and attenuation corrections with recovery correction showed an overall bias of -7.3% for the STR, -4.0% for BKG activity, and -7.8% for V(3)". TDCS corrections of phantom activities were relatively uniform for the 6 different collimators, with variabilities of <5.5% for the STR and <3.0% for BKG activities. TDCS correction of human (123)I-beta-CIT images was of a similar, although slightly larger, magnitude than for the phantom data, with increased V(3)" values of 9.4 +/- 2.3 and 4.9 +/- 0.6, with and without scatter correction, respectively., Conclusion: The TDSC method significantly improved the accuracy of SPECT images with a nonuniform distribution of activity highly concentrated in central regions. The value of V(3)" was significantly increased in phantom and human data, with most of the improvement derived from an increase in STR activity. This scatter correction method was approximately equally useful with data from the 6 different collimators and is recommended for more accurate quantitation of nonuniformly distributed brain activities.

Objectives: Accurate mu maps are important for quantitative image reconstruction in SPECT. The Compton scatter energy window (CSW) technique has been proposed to define the outline of objects. In this technique, a lower energy window image is acquired in addition to the main photo-peak energy window. The image of the lower energy window is used to estimate the edge of the scanned object to produce a constant attenuation map. The aim of this study was to investigate the dependency of CSW on the spatial and energy distribution of radioisotope to predict the edges of objects., Methods: Two particular cases of brain study were considered, namely uniform distribution and non-uniform distribution using Monte Carlo simulation and experiments with uniform cylindrical phantom and hotspot phantom. The phantoms were filled with water and a radioactive solution of 99mTc. For each phantom, 20%, 30%, 40% and 50% thresholds of the mean profile were applied to estimate Ewt, the energy window for minimum difference between the estimated and true edge of objects., Results: The Ewt's were 100-120 keV with a 40% threshold and 92-114 keV with a 30% threshold for uniform and hotspot phantoms, respectively., Conclusions: Edge of the objects with CSW technique varies with energy window and thresholds. Careful setting of the energy window is required to use the CSW technique.

The purpose of this study was to develop a reliable and practical strategy that generates quantitative CBF and OEF maps accurately from PET data sets obtained with 15O-tracers. Sequential sinogram data sets were acquired after the administration of 15O-tracers, and combined single-frame images were obtained. The delay time between sampled input function and the brain was estimated from the H2(15)O study with the whole brain and the arterial time-activity curves (TACs). The whole-brain TACs were obtained from the reconstructed images (image-base method) and the sinogram data (sinogram-base method). Six methods were also evaluated for the dead-time and decay correction procedures in the process of generating a single-frame image from the dynamic sinogram. The estimated delay values were similar with both the sinogram-based and image-based methods. A lumped correction factor to a previously added single-frame sinogram caused an underestimation of CBF, OEF and CMRO2 by 16% at maximum, as compared with the correction procedure for a short sinogram. This suggested the need for a dynamic acquisition of a sinogram with a short interval. The proposed strategy provided an accurate quantification of CBF and OEF by PET with 15O-tracers.