Effect of resolution improvement on required count density in ECT imaging: a computer simulation

The effects of changes in spatial resolution and total number of counts on image quality were investigated for positron and single photon emission computed tomography (ECT) systems. A variety of high contrast phantoms were generated in a computer simulation and count density and spatial resolution were varied independently over a wide range. As system spatial resolution is improved, significantly fewer counts are needed to give images of comparable visual quality. Using 100% object contrast, it was found that the number of counts could be reduced by a factor of four for a 2 mm improvement in spatial resolution over a wide range of parameters. This is due to the fact that image contrast increases rapidly with spatial resolution improvements in high contrast objects such as those used in this simulation and typically encountered in brain and cardiac ECT studies.     

Rodent brain imaging with SPECT/CT

We evaluated methods of imaging rat models of stroke in vivo using a single photon emission computed tomography (SPECT) system dedicated to small animal imaging (X-SPECT, Gamma Medica-Ideas, Northridge, CA). An animal model of ischemic stroke was developed for in vivo SPECT/CT imaging using the middle cerebral artery occlusion (MCAO) technique. The presence of cerebral ischemia was verified in ex vivo studies using triphenyltetrazolium chloride (TTC) staining. In vivo radionuclide imaging of cerebral blood flow was performed in rats following MCAO using dynamic planar imaging of 99mTc-exametazime with parallel hole collimation. This was followed immediately by in vivo radionuclide imaging of cerebral blood flow with 99mTc-exametazime in the same animals using 1-mm pinhole SPECT. Correlated computed tomography imaging was performed to localize radiopharmaceutical uptake. The animals were allowed to recover and ex vivo autoradiography was performed with separate administration of 99mTc-exametazime. Time activity curve of 99mTc-exametazime showed that the radiopharmaceutical uptake could be maintained for over 9 min. The activity would be expected to be relatively stable for a much longer period, although the data were only obtained for 9 min. TTC staining revealed sizable infarcts by visual observation of inexistence of TTC stain in infracted tissues of MCAO rat brains. In vivo SPECT imaging showed cerebral blood flow deficit in the MCAO model, and the in vivo imaging result was confirmed with ex vivo autoradiography. We have demonstrated a capability of imaging regions of cerebral blood flow deficit in MCAO rat brains in vivo using a pinhole SPECT dedicated to small animal imaging.     

Short-scan SPECT imaging with non-uniform attenuation and 3D distance-dependent spatial resolution

Image quality and quantitative accuracy in single-photon emission computed tomography (SPECT) can be degraded by, e.g., the effects of photon attenuation and finite spatial resolution. It is generally considered that adequate compensation for such effects on SPECT images requires data acquired over 2 pi. Recently, using the existing consistency condition on the data function, Noo and Wagner (2001 Inverse Problems 17 1357-72) have shown analytically that data acquired over only pi can be used to correct completely for the effect of uniform attenuation in SPECT. It remains unknown, however, whether data acquired only over pi in SPECT with non-uniform attenuation and/or 3D distance-dependent spatial resolution (DDSR) contain complete information for accurate image reconstruction. In this work, we develop a heuristic perspective, which is referred to as the potato peeler perspective to show conceptually that data in SPECT with non-uniform attenuation and/or 3D DDSR acquired over 2 pi contain redundant information and that such information can be used to reduce the scanning angle in SPECT. Specifically, we show heuristically that, in SPECT with only non-uniform attenuation, the scanning angle can be reduced from 2 pi to pi and that, in SPECT with both non-uniform attenuation and DDSR with a physically realistic form, the scanning angle can be reduced from 2 pi to pi in a practical sense. We conduct computer simulation studies, and the results from these studies corroborate the observations obtained based upon the heuristic potato peeler perspective.     

Model-based compensation for quantitative 123I brain SPECT imaging

Previously we have developed a model-based method that can accurately estimate downscatter contamination from high-energy photons in 123I imaging. In this work we combined the model-based method with iterative reconstruction-based compensations for other image-degrading factors such as attenuation, scatter, the collimator-detector response function (CDRF) and partial volume effects to form a comprehensive method for performing quantitative 123I SPECT image reconstruction. In the model-based downscatter estimation method, photon scatter inside the object was modelled using the effective source scatter estimation (ESSE) technique, including contributions from all the photon emissions. The CDRFs, including the penetration and scatter components due to the high-energy 123I photons, were estimated using Monte Carlo (MC) simulations of point sources in air at various distances from the face of the collimator. The downscatter contamination was then compensated for during the iterative reconstruction by adding the estimated results to the projection steps. The model-based downscatter compensation (MBDC) was evaluated using MC simulated and experimentally acquired projection data. From the MC simulation, we found about 39% of the total counts in the energy window of 123I were attributed to the downscatter contamination, which reduced image contrast and caused a 1.5% to 10% overestimation of activities in various brain structures. Model-based estimates of the downscatter contamination were in good agreement with the simulated data. Compensation using MBDC removed the contamination and improved the image contrast and quantitative accuracy to that of the images obtained from 159 keV photons. The errors in absolute quantitation were reduced to within +/-3.5%. The striatal specific binding potential calculated based on the activity ratio to the background was also improved after MBDC. The errors were reduced from -4.5% to -10.93% without compensation to -0.55% to 4.87% after compensation. The model-based method provided accurate downscatter estimation and, when combined with iterative reconstruction-based compensations, accurate quantitation was obtained with minimal loss of precision.     

Tc-99m-ECD SPECT brain imaging in children with Tourette's syndrome

We undertook this study to assess the patterns of regional cerebral perfusion (RCP) with SPECT using Technetium- 99m-ethyl cysteinate dimer (Tc-99m-ECD) in children with Tourette's Syndrome (TS), and to compare these with the patterns in a group of normal controls. The study sample consisted of 38 children (7 to 14 years) who met the ICD-10 and DSM/IV criteria for Tourette's Syndrome, and a control group of 18 children (9 to 14 years). The Children's Depression Inventory and Maudsley Obsessional-Compulsive Questionnaire were used for assessment, and the severity of motor and vocal tics were assessed using the Goetz Rating Scale. The RCP values were significantly lower in the TS group in left caudate, cingulum, right cerebellum, left dorsolateral prefrontal, and the left orbital frontal region. A positive correlation was found between the severity of vocal tics and blood flow of mid-cerebellum, right dorsolateral prefrontal and left dorsolateral prefrontal regions. Although no depressive or obsessive patients were included in the study, the depression and obsession scores were found to be negatively correlated with all RCP values, especially in the temporal regions. Further studies are needed to explore the relationship between the hypoperfusion of certain brain areas and the underlying neurophysiology and neurobiology of patients with TS. Additional disturbances such as obsessive-compulsive symptoms and depressive symptoms should also be assessed     

Spatial resolution in fast time-resolved transillumination imaging: an indeterministic Monte Carlo approach

The spatial resolution achievable in time-resolved optical transillumination imaging through a turbid (scattering and absorbing) medium has been reassessed theoretically. The temporal point spread function was constructed assuming a delta function input pulse, a approximately 50 mm thick medium and a small detector with zero risetime. Temporal profiles were derived from an indeterministic Monte Carlo simulation for different time scales. From the temporal point spread function (TPSF), an analytic edge response function from which the spatial resolution was determined was derived. Previous analytical methods for determining the spatial resolution are approximations for very short flight times (sub-100 ps time region). The results show that a spatial resolution of about two millimetres is possible under ideal signal-to-noise ratio conditions and with detector gate times of the order of ten picoseconds. If this predicted spatial resolution can be achieved in an imaging system, it may be possible to improve the diagnosis of breast tumours.     

Spatial resolution requirements for acquisition of the virtual screening slide for digital whole-specimen breast histopathology

We examined the effect of lateral spatial resolution and reader specialty on the accuracy of detection of breast cancer. The motivation for this pilot study was the need to acquire and display very large data sets in whole-specimen 3D digital breast histopathology imaging. The ultimate goal is to determine the minimum resolution adequate for detection of malignancy. Twenty-three histologic slides were selected from breast pathology cases and digitized at 2 sampling distances (3.2 and 1.9 microm pixels). Images were viewed by 14 pathologists, of whom 5 had breast pathology as their primary specialty. The readers assessed the likelihood of malignancy on a 5-point Likert scale, and provided a provisional diagnosis. For the detection task, sensitivity, specificity, overall accuracy of detection, and area under the receiver-operator curve were calculated. An overall diagnostic score, and scores grouped by malignancy type, were also computed. Outcome measures were examined for significant resolution and specialty effects. Increasing the lateral resolution significantly improved accuracy in diagnosis (P=.004) but no effect was found for detection. Breast specialists achieved significantly higher scores for all outcome measures except specificity. Differences in performance between the 2 groups of readers tended to be greater for the diagnostic task compared to detection, especially at the higher resolution. However, specimen coverage may also be a significant factor. Factors related to the readers may have also affected performance in this study. Based on these results, a more comprehensive study should examine pixel sizes between 0.7 and 1.9 microm.     

The effect of acquisition interval and spatial resolution on dynamic cardiac imaging with a stationary SPECT camera

The current SPECT scanning paradigm that acquires images by slow rotation of multiple detectors in body-contoured orbits around the patient is not suited to the rapid collection of tomographically complete data. During rapid image acquisition, mechanical and patient safety constraints limit the detector orbit to circular paths at increased distances from the patient, resulting in decreased spatial resolution. We consider a novel dynamic rotating slant-hole (DyRoSH) SPECT camera that can collect full tomographic data every 2 s, employing three stationary detectors mounted with slant-hole collimators that rotate at 30 rpm. Because the detectors are stationary, they can be placed much closer to the patient than is possible with conventional SPECT systems. We propose that the decoupling of the detector position from the mechanics of rapid image acquisition offers an additional degree of freedom which can be used to improve accuracy in measured kinetic parameter estimates. With simulations and list-mode reconstructions, we consider the effects of different acquisition intervals on dynamic cardiac imaging, comparing a conventional three detector SPECT system with the proposed DyRoSH SPECT system. Kinetic parameters of a two-compartment model of myocardial perfusion for technetium-99m-teboroxime were estimated. When compared to a conventional SPECT scanner for the same acquisition periods, the proposed DyRoSH system shows equivalent or reduced bias or standard deviation values for the kinetic parameter estimates. The DyRoSH camera with a 2 s acquisition period does not show any improvement compared to a DyRoSH camera with a 10 s acquisition period.     

Model-based crosstalk compensation for simultaneous 99mTc/123I dual-isotope brain SPECT imaging

In this work, we developed a model-based method to estimate and compensate for the crosstalk contamination in simultaneous 123I and 99mTc dual isotope brain single photo emission computed tomography imaging. The model-based crosstalk compensation (MBCC) includes detailed modeling of photon interactions inside both the object and the detector system. In the method, scatter in the object is modeled using the effective source scatter estimation technique, including contributions from all the photon emissions. The effects of the collimator-detector response, including the penetration and scatter components due to high-energy 123I photons, are modeled using precalculated tables of Monte Carlo simulated point-source response functions obtained from sources in air at various distances from the face of the collimator. The model-based crosstalk estimation method was combined with iterative reconstruction based compensation to reduce contamination due to crosstalk. The MBCC method was evaluated using Monte Carlo simulated and physical phantom experimentally acquired simultaneous dual-isotope data. Results showed that, for both experimental and simulation studies, the model-based method provided crosstalk estimates that were in good agreement with the true crosstalk. Compensation using MBCC improved image contrast and removed the artifacts for both Monte Carlo simulated and experimentally acquired data. The results were in good agreement with images acquired without any crosstalk contamination.     

EEG assessment of brain activity: Spatial aspects,segmentation and imaging

High temporal resolution and sensitivity to index different functional brain states makes the EEG a powerful tool in psychophysiology. Its full potential can now be utilized since recording technology and computational power for the large data masses has become affordable. However, basic traditional strategies in EEG need reviewing.Conventional, spontaneous or evoked EEG traces which are used for various complex analyses give ambiguous information on EEG power (amplitude) and phase for a given point on the scalp. Principally, analysis should first be done over space, then over time, to avoid ambiguities or pre-selections. First or second spatial derivative computations can provide “reference-free” data for analyses over time. We propose to use direct, spatial approaches for the analysis of the scalp EEG field distributions when simultaneous recording in several EEG channels can be examined.The ambiguity of the conventional EEG waveshapes results in different, equally “correct” scalp maps of EEG power of the same multichannel data for different reference electrodes. An exeption are scalp maps of EEG power computed against the common, average reference, as they are related to the reference-free spatial distribution (maps) of the maximal and minimal (extreme) field values over time, and thus are directly interpretable in terms of net orientation of the generator process.A proposed, reference-free EEG segmentation into epochs of periodically stationary spatial distributions of the mapped scalp EEG fields uses the locations of maximal and minimal (extreme) field values at each moment in time as classifiers, and thus avoids the priviledging of two arbitrarily chosen recording points in the field.     

Neuroanatomy of the fragile X knockout mouse brain studied using in vivo high resolution magnetic resonance imaging.

Magnetic resonance imaging (MRI) of the brain of fragile X patients, the most frequent form of inherited mental retardation, has revealed abnormalities in the size of specific brain structures, including the cerebellar vermis, the hippocampus, and the ventricular system. We intended to quantify the differences observed in the patient studies in the fragile X knockout mouse model, which is a good model for the disease, paralleling the human disorder in having cognitive deficits, macro-orchidism, and immature dendritic spines. Therefore we set up MRI of the mouse brain which allowed us to measure the size of the brain structures reported to be abnormal in human fragile X patients in the mouse model. We did not find evidence for size alterations in various brain regions of the fragile X mouse model, but the method described may find a wide application in the study of mutant mouse models with neurological involvement.     

Functional imaging of the brain using single photon emission computerized tomography (SPECT)

Summary The use of tracers is an important technique available for studying cerebral function. Changes in signal are large, but as a result of its photon limited nature, the measurement of this signal is limited: spatially, temporally and in terms of accuracy. The most commonly used single photon (SPECT) system (as apposed to positron) is that with a rotating gamma camera, although multi-headed devices and special purpose rings are now also commonly available. The problems of obtaining good functional information are however identical. Firstly the devices need to be optimised in terms of resolution and sensitivity. Secondly several sources of error, notably those associated with scatter, attenuation and limited spatial resolution, need to be corrected, with the aim of obtaining quantitative estimates of radioactivity concentration. Finally such quantitative estimates need to be converted into meaningful estimates of physiological variables by use of an appropriate model. The general aim of many SPECT measurements is to estimate blood flow for example using Tc-99m labelled HMPAO as a tracer. Good results have been obtained in many clinical conditions: stroke, dementia, tumour and epilepsy, for example. Many other tracers are also available, for example to measure density of receptor sites. The use of SPECT in conjunction with other techniques after image registration is suggested as being an essential tool in extracting maximal clinical information.     

18F-FDG SPECT/CT脑显像诊断老年性痴呆初步应用

目的探讨老年性痴呆（AD）的^18F—FDGSPECT／CT显像图特点。方法10例AD患者、10例血管性痴呆（VD）患者及20例正常对照行^18F—FDGSPECT／CT脑显像。患者禁食6h以上，戴眼罩安静休息20min后肘静脉注射^18F—FDG185—296MBq，60min后开始SPECT和X线CT透射扫描。先进行X线透射扫描，CT连续采集10min，然后进行符合线路PET连续采集30min。透射和发射图像进行衰减校正和叠代重建（COSEM），得到横断面、冠状面、矢状面及其CT与SPECT的融合图像。半定量分析取横断面图像，在双侧顶叶、颢叶、额叶和小脑划取感兴趣区（ROI），并获取单位像素放射性计数。将各脑叶分别与同侧小脑进行比较，即可得放射性摄取比值（Rcl／cb）。结果对10例患者、10例VD患者和20例正常对照的^18F-FDG显像图进行X线衰减校正前后比较和与CT扫描图的同机图像融合。结果表明，经过X线衰减校正后的^18F—FDG正电子图像比校正前的图像明显清晰，校正后的图像由发散、模糊变为细腻、清晰。融合后的图像与融合前的图像比较，在解剖学定位方面有了很大的改善，特别表现在大脑的沟回、基底节的辨认方面。在10例AD患者中，图像呈双侧颞叶、额叶或顶叶对称性放射性摄取减低者8例，占80％。图像呈单侧额叶或顶叶放射性减低者2例，占20％。在10例VD患者中，图像均呈多发性非对称性放射性稀疏区，且部位可位于基底节、丘脑或脑皮质区。AD组双侧顶叶、额叶和颞叶与同侧小脑的放射性摄取比值（Rcl／cb）明显低于正常对照组（P〈0．01）。结论AD患者的特征性^18F—FDG显像图改变对于AD的诊断及与VD的鉴别诊断有十分重要的临床意义。     

Spatial resolution of magnetic resonance imaging Fricke-gel dosimetry is improved with a honeycomb phantom

The spatial accuracy of magnetic resonance imaging (MRI) Fricke-gel dosimetry is limited by diffusion of ferric ions. This paper describes a honeycomb structure to limit diffusion of Fe3+ ions in a three-dimensional phantom. Such a phantom containing the dosimeter gel was irradiated to a known dose distribution. Maps of dose distributions were produced from the MR images acquired at 2 and 24 hours after the dose was given. The dose distribution maps verified that the honeycomb structure precludes ion diffusion from one honeycomb cell to another, thus improving the usefulness of MRI Fricke-gel dosimetry.     

皮质下梗塞所致失语的SPECT显像研究

目的探讨皮质下梗塞所致失浯的发生与脑血流改变的部位、范围及程度间的关系。方法对37例临床确诊为单侧皮质下梗塞的患者行SPECT局部脑血流显像，判定局部脑血流（rCBF）改变的部位、范围及程度，并按北京大学人民医院汉语成套测验（aphasia battery of Chinese，ABC）进行检测。结果30例有失语表现，SPECT显像示患者的rCBF降低部位多位于基底节区前部、上部、外侧部及丘脑。皮质下失语的患者rCBF降低部位多累及大脑皮质语言功能区（x^2=8．87，P〈0．005）。病灶区的rCBF及rCBF降低的百分比与失语程度的相关系数分别为-0．41（t=-1．59，P〉0．05）和0．64（t=2．71，P〈0.05）；病灶的范围、病灶数与失语程度之间的相关系数分别为0．79（t=3．81，P〈0．01）和0．67（t=3．16，P〈0．01）。结论皮质下梗塞所致失语患者rCBF降低部位多累及大脑皮质语言功能区；病灶区的rCBF与失语程度的相关性较小，而病灶的rCBF降低的百分比、病灶范围、病灶数与失语程度呈正相关。     

Clinical objectives, tracer constraints and technological requirements for in vivo imaging.

The aim of this paper is to identify future directions for developing instrumentation to measure the tissue kinetics of tracers labelled with positron emitting isotopes. A principal theme developed is the need to realise increased sensitivity for detection. In order to present the case for these improvements, examples are shown of current procedures which would improve with increased sensitivity.     

Computer phantom study of brain PET glucose metabolism imaging using a rotating SPECT/PET camera

Positron emission tomography (PET) with [18F] fluoro-deoxy-glucose (FDG) provides information about glucose metabolism and is used to measure tissue glucose kinetics in the brain. The recent interest in hybrid SPECT/PET systems emerged as a practical approach to reduce the high cost of purchasing a dedicated ring-detector PET system. We have implemented interpolation methods for processing the projection data that could potentially reduce artifacts when reconstructing a dynamic imaging sequence in a PET study from a dual-head rotating SPECT/PET system. The computer simulations predict that parameter estimates from the dedicated PET system will be superior to results using the rotating camera system. However, the rotating camera system using projection interpolation may approach the accuracy of the dedicated PET system if the data noise is below 20%.     

Multicolor in vivo time-lapse imaging at cellular resolution by stereomicroscopy.

Intravital time-lapse imaging has altered significantly many long-standing rules of biological mechanisms, but being apparatus-intense and laborious, time-lapse imaging remained mostly restricted to specialized labs. We show that recently introduced, fully automated fluorescence stereomicroscopes represent cost-effective but powerful means of imaging dynamic events ranging from observing embryogenesis over several days to detailed tissue rearrangements and fast blood cell rolling in vivo. When combined with deconvolution approaches, even subcellular resolution in several colors can be achieved. Using three-dimensional image recording, we show the spatial reconstruction of expression patterns. Furthermore, by combining three-dimensional image recording over time with subsequent deconvolution analysis, we demonstrate that subcellular dynamics such as axonal pathfinding can be resolved. These findings promise that time-lapse imaging using a stereomicroscope will become a hands-on standard method for phenotype analysis in many fields of biology.     

The requirements of the brain for some amino acids.

1. A constant specific activity of radioactively labelled amino acids was maintained in the circulation by means of a new technique devised for this purpose. This has made it possible to measure accurately the entry rates of amino acids into the brain in vivo. 2. The rates of entry into the brain of seven nutritionally non-essential amino acids were measured. 3. Glycine and proline enter the brain relatively slowly, at rates comparable to those of amino acids which are not normally found in the blood. Thus their entry is due mainly if not entirely to passive diffusion. 4. Serine (which is used by the brain to make glycine) and alanine (which is used to make glutamate and aspartate) enter the brain as rapidly as the essential amino acids and thus, although not essential for the body as a whole, appear to be essential for the brain. 5. It is suggested that those amino acids that the brain is able to synthesize have low rates of entry, even though they are present at high concentrations in the plasma, but that the transport systems for those amino acids that are not synthesized in the brain ensure rapid entry at rates that are related to the rates of cerebral utilization.     

Temporal resolution requirements for intensity modulated radiation therapy delivered by multileaf collimators.

Intensity modulated radiation therapy may be delivered via dynamic control of a multileaf collimator by defining dynamic leaf trajectories at a series of control points which are spaced at arbitrary intervals throughout an exposure. Leaves move linearly between the positions defined at the control points and hence leaf motion is a linear approximation to the planned trajectories. When many control points are used, very complex modulations can be defined accurately. If too few are used, dose errors are introduced which depend on the complexity of the modulation and the number of control points chosen. Proposed intensity modulations, of varying complexity, have been converted to trajectory plans where the number of equally spaced control points varied between 11 and 99. In each case the fluence map generated by the resulting leaf motions was computed, and this was quantitatively compared with the desired modulation by calculating the root mean square (RMS) error. It is shown that in no case can the RMS error be significantly reduced by increasing the number of control points beyond 50. Guidelines are derived such that compensators and simple modulations may be very accurately delivered with about 20 control points, moderately complex modulations require 30-35 control points and very complex modulations 50 control points. A similar analysis of the step and shoot technique suggests that very accurate deliveries are always achieved with a maximum of 25 equally weighted static fields and reasonable accuracy with 15 fields.