Preclinical Single-photon Emission Computed Tomography Research Articles

Performance Evaluation of a Preclinical SPECT Scanner with a Collimator Designed for Medium-Sized Animals.

Background Equipped with two stationary detectors, a large bore collimator for medium-sized animals has been recently introduced for dedicated preclinical single-photon emission computed tomography (SPECT) imaging. We aimed to evaluate the basic performance of the system using phantoms and healthy rabbits. Methods A general-purpose medium-sized animal (GP-MSA) collimator with 135 mm bore diameter and thirty-three holes of 2.5 mm diameter was installed on an ultrahigh-resolution scanner equipped with two large stationary detectors (U-SPECT5-E/CT). The sensitivity and uniformity were investigated using a point source and a cylinder phantom containing 99mTc-pertechnetate, respectively. Uniformity (in %) was derived using volumes of interest (VOIs) on images of the cylinder phantom and calculated as [(maximum count − minimum count)/(maximum count + minimum count) × 100], with lower values of % indicating superior performance. The spatial resolution and contrast-to-noise ratios (CNRs) were evaluated with images of a hot-rod Derenzo phantom using different activity concentrations. Feasibility of in vivo SPECT imaging was finally confirmed by rabbit imaging with the most commonly used clinical myocardial perfusion SPECT agent [99mTc]Tc-sestamibi (dynamic acquisition with a scan time of 5 min). Results In the performance evaluation, a sensitivity of 790 cps/MBq, a spatial resolution with the hot-rod phantom of 2.5 mm, and a uniformity of 39.2% were achieved. The CNRs of the rod size 2.5 mm were 1.37, 1.24, 1.20, and 0.85 for activity concentration of 29.2, 1.0, 0.5, and 0.1 MBq/mL, respectively. Dynamic SPECT imaging in rabbits allowed to visualize most of the thorax and to generate time-activity curves of the left myocardial wall and ventricular cavity. Conclusion Preclinical U-SPECT5-E/CT equipped with a large bore collimator demonstrated adequate sensitivity and resolution for in vivo rabbit imaging. Along with its unique features of SPECT molecular functional imaging is a superior collimator technology that is applicable to medium-sized animal models and thus may promote translational research for diagnostic purposes and development of novel therapeutics.

In vivo absolute quantification of striatal and extrastriatal D2/3 receptors with [123I]epidepride SPECT

Background[123I]epidepride is a high-affinity radiotracer used in single-photon emission computed tomography (SPECT) imaging of the D2/3 receptors. It binds with high affinity to striatal and extrastriatal receptors. Nevertheless, its slow kinetics in the striatum impedes quantification in this region. Thus, an approach that would allow a simultaneous quantification of both striatal and extrastriatal D2/3 receptors would be of interest for preclinical and clinical SPECT neuroimaging. We describe a partial saturation protocol that allows us to produce an in vivo Scatchard plot and thus estimate Bavail and appKd separately in both striatal and extrastriatal regions, through a single dynamic SPECT session. To validate this approach, a multi-injection protocol is used for the full kinetic modeling of [123I]epidepride using a two-tissue compartment, 5-parameter model (2T-5k).MethodsEighteen male rats were used. Binding parameters were estimated using the multi-injection protocol. Various simulations were performed to estimate the optimal conditions for the partial saturation protocol, which was applied at the region and voxel level. The results of the partial saturation study were compared to those obtained with the 2T-5k model. To illustrate the interest of the partial saturation approach, we performed a preliminary study of the effect of a chronic, subcutaneous administration of haloperidol (1 mg/kg/day), a D2 receptor antagonist, on the Bavail of [123I]epidepride in the rat striatum.ResultsA series of simulations demonstrated that a mass of 3 ug/kg of unlabeled epidepride allows the formation of an in vivo Scatchard plot. The partial saturation study led to robust estimations of Bavail in all brain regions that highly correlated (r = 0.99) with the corresponding values from the multi-injection study. A chronic haloperidol treatment resulted in a 17.9% increase in the Bavail values in the left Caudate Putamen nucleus (CP) (p = 0.07) and a 13.8% increase in the right CP (p = 0.12).ConclusionA partial saturation method allowed the robust quantification of D2/3 receptors in striatal and extrastriatal D2/3 receptors with a single-scan approach. This approach may be applied in the mapping of the D2/3 receptor in translational biological studies and potentially, in clinical SPECT imaging.

Preclinical SPECT Imaging of Choroidal Neovascularization in Mice Using Integrin-Binding [99mTc]IDA-D-[c(RGDfK)]2.

Integrin ɑvβ3, an adhesion molecule overexpressed in neovascular endothelial cells, is involved in ocular angiogenesis. Integrin ɑvβ3-binding arginine-glycine-aspartic acid (RGD) peptide has been used to target and visualize new vessels. We explored the use of integrin ɑvβ3-targeted RGD peptide ([99mTc]IDA-D-[c(RGDfK)]2) for in vivo molecular imaging of choroidal neovascularization (CNV). To induce CNV in animals, the right eyes of C57BL/6 mice were treated with retinal argon laser photocoagulation. CNV formation was confirmed on immunohistopathological examination of retinal and choroidal tissues. To explore the association of integrin with angiogenesis, integrin mRNA expression in the retinal and choroidal tissues was measured using real-time reverse transcriptase-polymerase chain reaction. For in vivo imaging, mice were intravenously injected with [99mTc]IDA-D-[c(RGDfK)]2 and single-photon emission computed tomography (SPECT) images of [99mTc]IDA-D-[c(RGDfK)]2 were obtained before laser induction (baseline) and at 1, 3, 7, and 14days post-induction. CNV-induced regional alterations were measured using radiotracer uptake count. Immunohistopathological examination revealed that CNV lesions showed intense fluorescein isothiocyanate (FITC)-D-[c(RGDfK)]2 immunofluorescence, in contrast to the normal retina and choroid. Retinal integrin mRNA expression peaked at day 1 following CNV induction. On SPECT images using [99mTc]IDA-D-[c(RGDfK)]2, the radio-uptake count in eyes with CNV was significantly higher than in normal controls on days 1-7 (all p < 0.05), with a peak at day 3 representing the highest angiogenic activity. Our preclinical data demonstrated that [99mTc]IDA-D-[c(RGDfK)]2 can detect CNV and its associated angiogenesis in an animal model of CNV. SPECT imaging using an integrin ɑvβ3-targeted RGD peptide radiotracer may be a useful tool for in vivo functional molecular imaging of CNV.

Simulation study of a novel target oriented SPECT design using a variable pinhole collimator.

In the past decade, demands for organ specific (target oriented) single-photon emission computed tomography (SPECT) is increasing, and several groups have conducted studies on developing clinical dedicated SPECT with pinhole collimator to improve the spatial resolution. However, acceptance angle of the collimator cannot be adjusted to fit the different ROIs of target objects because the shape of pinhole could not be changed, and the magnifying factor cannot be maximized as the collimator-to-detector distance is fixed. Furthermore, those dedicated pinhole SPECTs are typically made for a single purpose and therefore possess a drawback in that it cannot be utilized for any other purpose. In this study, we propose a novel SPECT system using variable pinhole collimator (VP SPECT) whose parameters are flexible. The proposed variable pinhole collimator is modeled on conventional pinhole by piling several tungsten layers of different apertures. Depending on the combination of the holes in each layer, a variety of hole diameters and acceptance angles of the pinhole can be made. In addition, VP SPECT system allows attaching the collimator to the object as close as possible to maximize the sensitivity and adjust the distance of the pinhole from the scintillation detector to optimize the system resolution for each rotation angle, automatically. For quantitative measurement, we compared the sensitivity and spatial resolution of VP SPECT with those of conventional pinhole SPECT. To determine the possibility of the clinical and preclinical use of proposed system, a digital mouse whole-body (MOBY) phantom is used for simulating the live mouse model. The result of simulation using ultra-micro hot spot phantom shows that the sensitivity of the proposed VP SPECT system is about 297% of that of the conventional system. While hot rods of diameter 0.6mm can be distinguished in the image with the proposed VP SPECT system, 1.2-mm hot rods are barely discernible in the conventional pinhole SPECT image. According to the result of MOBY phantom simulation, heart walls separated by 3mm were not distinguished in conventional pinhole SPECT images, but were clearly discerned in VP SPECT images. In this study, we designed a novel pinhole collimator for SPECT and presented preliminary results of target oriented imaging with a simulation study. Currently, we are pursuing strategies to realize the proposed system, with the goal to apply the technology into a high-sensitivity and high-resolution preclinical SPECT. Should VP SPECT be applied to the clinical setting, we anticipate a high-sensitivity, high-resolution system for applications such as heart dedicated SPECT or related fields.

Preclinical PET, SPECT, CT, MRI and optical imaging in cancer research: An overview

Cancer research is primarily dependent on rodent models. There has been a huge advancement in anticancer drug discovery in the last two decades, which is mainly due to improved animal models and introduction of non-invasive imaging technologies. Non-invasive imaging technology plays an important role in cancer and other biomedical research areas including neurology, cardiology, nanotechnology and stem cell biology. The intricate pathways in cancer initiation, progression and metastasis can be visualized and the processes can be analyzed quantitatively using these techniques. Robust preclinical data is the backbone of anticancer drug discovery, which can be obtained precisely using imaging technology. This review is focused on the dedicated preclinical imaging modalities such as Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), X-ray Computed Tomography (CT), Magnetic Resonance Imaging (MRI), Optical imaging and Cerenkov imaging. This paper discusses their present roles in basic and translational research towards evaluation of suitability of target molecules for further clinical trials.The unique features of the imaging modalities enable them to provide information necessary for understanding structural, functional and molecular processes involved in various stages of cancer development thus bridging the gap between bench and bedside.

A Numerical Study of Different Types of Collimators for a High-Resolution Preclinical CdTe Pixelated Semiconductor SPECT System

In single-photon-emission computed tomography (SPECT) with a pixelated semiconductor detector (PSD), not only pinhole collimators but also parallel-hole collimators are often used in preclinical nuclear-medicine imaging systems. The purpose of this study was to evaluate and compare pinhole and parallel-hole collimators in a PSD. For that purpose, we paired a PID 350 (Ajat Oy Ltd., Finland) CdTe PSD with each of the four collimators most frequently used in preclinical nuclear medicine: (1) a pinhole collimator, and (2) low-energy high-resolution (LEHR), (3) low-energy general-purpose (LEGP), and (4) low-energy high-sensitivity (LEHS) parallel-hole collimators. The sensitivity and spatial resolution of each collimator was evaluated using a point source and a hot-rod phantom. The highest sensitivity was achieved using LEHS, followed by LEGP, LEHR, and pinhole. Also, at a source-to-collimator distance of 2 cm, the spatial resolution was 1.63, 2.05, 2.79, and 3.45 mm using pinhole, LEHR, LEGP, and LEHS, respectively. The reconstructed hot-rod phantom images showed that the pinhole collimator and the LEHR parallel-hole collimator give a fine spatial resolution for preclinical SPECT with PSD. In conclusion, we successfully compared different types of collimators for a preclinical pixelated semiconductor SPECT system.

Cardiovascular preclinical imaging.

Non-invasive imaging in the form of single-photon emission-computed tomography (SPECT), positron-emission tomography (PET), computed tomography (CT), echocardiography or magnetic resonance imaging (MRI) is a very useful tool for cardiovascular research as it allows assessment of biological processes in vivo. Nuclear imaging with SPECT and PET offers the advantage of high sensitivity, the potential for serial imaging, and reliable quantification. Currently a wide range of established as well as innovative agents is available and can be imaged with dedicated preclinical and clinical SPECT and PET imaging systems. These scanners can be equipped with CT and MRI components to form hybrid imaging systems. This review provides an outline on SPECT and PET as capable tools for translational research in cardiology as part of a workflow similar to the one used in clinical imaging illustrating the concept "from bench to bedside".

Design of a dual-resolution collimator for preclinical cardiac SPECT with a stationary triple-detector system.

One approach to preclinical single-photon emission computed tomography (SPECT) imaging that provides both high resolution and high sensitivity is based on imaging a mouse inside a collimating tube; many magnified pinhole projection images from a small target region, e.g., the heart, can be recorded simultaneously on multiple detectors with little multiplexing since each pinhole aperture's opening angle is restricted to view mostly the target organ. However, to obtain complete data for reconstruction, it may be necessary to scan the mouse through the target region of the tube. The authors are developing a different approach based on acquisition and reconstruction of both low-resolution and high-resolution projection data acquired sequentially through many pinholes embedded in two tungsten tube sections of different diameters, a "scout" section and a high-resolution section, placed end-to-end along the axis of a triple-head clinical SPECT scanner. This paper describes the design procedures used to determine the geometric parameters of two new collimator-tube sections, as well as one approach for joint reconstruction of data acquired from both sections. The high-resolution section was designed by projecting as many pinhole views of a simulated mouse heart as possible over each detector's camera, with no overlapping of heart projections and minimal overlapping between adjacent "hot" organ and cardiac projections. The authors then jointly optimized the geometric design of the scout section for a triple-detector camera system, as well as the number of maximum-likelihood expectation maximization (MLEM) iterations required to provide minimum mean-squared error of reconstructed voxel counts throughout a 7-cm axial range, with the constraints of fixed, 2.4-mm scout system resolution at the tube center for all apertures, limited multiplexing, and no detector motion. Simulated mouse projection data from both tube sections were then reconstructed to illustrate a simple approach for using high-resolution data to improve the whole-body scout images within a cylindrical region surrounding the heart. The 2-cm-inner-radius high-resolution tube section accommodated 87 platinum-iridium pinhole inserts, each with a 0.3-mm square aperture; their radial distances from the centerline of the system ranged from 2.2 to 3.0 cm. The optimal radial distance to the closest scout pinhole and optimal number of MLEM iterations were 4.4 cm and 35 iterations, respectively, and the radial distances of the 39 scout pinholes ranged from 4.4 to 4.8 cm; aperture sizes ranged from 1.1 to 1.7 mm transaxially and 0.9-1.5 mm axially. After including data from the high-resolution section viewing the heart region into whole-body mouse reconstructions from scout data, the authors obtained high-resolution images of the heart, embedded within lower resolution images of the body, with minimal artifacts. The authors have optimized a dual-resolution collimator tube that provides both whole-body projections of a mouse and more targeted projections centered on the heart that can be jointly reconstructed to obtain high-resolution images of the heart embedded within lower-resolution whole-body images.

In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.

The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10.

Iodine-131 imaging using 284 keV photons with a small animal CZT-SPECT system dedicated to low-medium-energy photon detection.

Iodine-131 is widely used for radionuclide therapy because of its β-particle and for diagnostic imaging employing its principal gamma ray. Since that principal gamma ray has the relatively high energy of 364 keV, small animal single-photon emission computed tomography (SPECT) imaging systems may be required to possess the ability to image such higher energy photons. The aim of this study was to investigate the possibility of imaging I-131 using its 284 keV photons instead of its 364 keV photons in a small animal SPECT imaging system dedicated to the detection of low-medium-energy photons (below 300 keV). The imaging system used was a commercially available preclinical SPECT instrument with CZT detectors that was equipped with multi-pinhole collimators and was accompanied by a CT imager. An energy window for I-131 imaging was set to a photopeak of 284 keV with a low abundance compared with 364 keV photons. Small line sources and two mice, one of each of two types, that were injected with NaI-131 were scanned. Although higher counts occurred at the peripheral region of the reconstructed images due to the collimator penetration by the 364 keV photons, the shape of the small line sources could be well visualized. The measured spatial resolution was relatively poor (~1.9 mm for full width at half maximum and ~3.9 mm for full width at tenth maximum). However, a good linear correlation between SPECT values and the level of I-131 radioactivity was observed. Furthermore, the uptake of NaI-131 to the thyroid gland for the two mice was clearly identified in the 3D-SPECT image fused with the X-ray CT image. We conclude that the use of an energy window set on the photopeak of 284 keV and the multi-pinhole collimator may permit I-131 imaging for a preclinical CZT-SPECT system that does not have the ability to acquire images using the 364 keV photons.

Evaluation of quantitative accuracy in CZT-based pre-clinical SPECT for various isotopes

In vivo pre-clinical single-photon emission computed tomography (SPECT) is a valuable tool for functional small animal imaging, but several physical factors, such as scatter radiation, limit the quantitative accuracy of conventional scintillation crystal-based SPECT. Semiconductor detectors such as CZT overcome these deficiencies through superior energy resolution. To our knowledge, little scientific information exists regarding the accuracy of quantitative analysis in CZT-based pre-clinical SPECT systems for different isotopes. The aim of this study was to assess the quantitative accuracy of CZT-based pre-clinical SPECT for four isotopes: 201Tl, 99mTc, 123I, and 111In. The quantitative accuracy of the CZT-based Triumph X-SPECT (Gamma-Medica Ideas, Northridge, CA, U.S.A.) was compared with that of a conventional SPECT using GATE simulation. Quantitative errors due to the attenuation and scatter effects were evaluated for all four isotopes with energy windows of 5%, 10%, and 20%. A spherical source containing the isotope was placed at the center of the air-or-water-filled mouse-sized cylinder phantom. The CZT-based pre-clinical SPECT was more accurate than the conventional SPECT. For example, in the conventional SPECT with an energy window of 10%, scatter effects degraded quantitative accuracy by up to 11.52%, 5.10%, 2.88%, and 1.84% for 201Tl, 99mTc, 123I, and 111In, respectively. However, with the CZT-based pre-clinical SPECT, the degradations were only 9.67%, 5.45%, 2.36%, and 1.24% for 201Tl, 99mTc, 123I, and 111In, respectively. As the energy window was increased, the quantitative errors increased in both SPECT systems. Additionally, the isotopes with lower energy of photon emissions had greater quantitative error. Our results demonstrated that the CZT-based pre-clinical SPECT had lower overall quantitative errors due to reduced scatter and high detection efficiency. Furthermore, the results of this systematic assessment quantifying the accuracy of these SPECT for various isotopes will provide valuable reference information for the design of CZT-based pre-clinical SPECT system imaging protocols.

Impact of injection dose, post-reconstruction filtering, and collimator choice on image quality of myocardial perfusion SPECT using cadmium-zinc telluride detectors in the rat.

BackgroundThe aims of this study were (1) to evaluate the impact of injection dose, post-reconstruction filtering, and collimator choice on image quality of myocardial perfusion single-photon emission computed tomography (SPECT) using cadmium-zinc telluride (CZT) detectors and (2) to determine how these factors affect measured infarct size in the in vivo rat.MethodsTwenty-four healthy and eight myocardial infarct (MI) rats underwent myocardial perfusion SPECT imaging after injection of various doses (25 to 200 MBq) of 99mTc-tetrofosmin using a standard (STD) five-pinhole collimator and high-sensitivity (HS) five-pinhole collimator. Image quality score, contrast-to-noise ratio, sharpness index, coefficient of variation (CV), and measured defect size were assessed as measures of image quality.ResultsThe image quality score increased and CV decreased as a function of injection dose. The contrast-to-noise ratio increased and sharpness index decreased as a function of Gaussian kernel size. When STD and HS were compared, HS tended to show higher image quality score and lower CV than STD. The use of post-reconstruction filter significantly improved image quality score and lessened CV. The reproducibility of defect size measurements, as assessed by intraclass correlation coefficients (ICC), between the collimators was poor-to-moderate (ICC = −0.31~0.57) with low (25 MBq) injection dose and with no or light (1.5-mm kernel size) filtering, whereas it was good-to-excellent (ICC = 0.75~0.97) with high (200 MBq) dose or low dose with heavy (2.5-mm kernel size) filtering. The filtering-related reproducibility was poor (ICC = −0.18~0.17) for STD with low injection dose, whereas it was good-to-excellent (ICC = 0.79~0.89) for HS. Furthermore, there was a filtering-related underestimation of defect size particularly with the use of heavy smoothing.ConclusionsAppropriate imaging setting is important to obtain high quality images and thereby reliable measurements using a preclinical myocardial SPECT in the rat. When only a low injection dose (25 MBq) is allowed, we would recommend to use HS with light (1.5-mm kernel size) filtering.

U-SPECT-BioFluo: an integrated radionuclide, bioluminescence, and fluorescence imaging platform.

BackgroundIn vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. However, to date these signatures are evaluated separately on individual preclinical systems. In this paper, we introduce a fully integrated bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics and image fusion, this integration can help improve understanding of the optical imaging (OI) results.MethodsAn OI module was developed for a preclinical SPECT system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the module for bioluminescence and fluorescence imaging was evaluated in both a phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A combination of a fluorescent dye and radioactive moiety was used to directly relate the optical images of the module to the SPECT findings. Bioluminescence imaging (BLI) was compared to the localization of the fluorescence signal in the tumors.ResultsBoth the phantom and in vivo mouse studies showed that superficial fluorescence signals could be imaged accurately. The SPECT and bioluminescence images could be used to place the fluorescence findings in perspective, e.g. by showing tracer accumulation in non-target organs such as the liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor spread (bioluminescence).ConclusionsWe developed a fully integrated multimodal platform that provides complementary registered imaging of bioluminescent, fluorescent, and SPECT signatures in a single scanning session with a single dose of anesthesia. In our view, integration of these modalities helps to improve data interpretation of optical findings in relation to radionuclide images.

Adaptive SPECT imaging with crossed-slit apertures.

Preclinical single-photon emission computed tomography (SPECT) is an essential tool for studying the progression, response to treatment, and physiological changes in small animal models of human disease. The wide range of imaging applications is often limited by the static design of many preclinical SPECT systems. We have developed a prototype imaging system that replaces the standard static pinhole aperture with two sets of movable, keel-edged copper-tungsten blades configured as crossed (skewed) slits. These apertures can be positioned independently between the object and detector, producing a continuum of imaging configurations in which the axial and transaxial magnifications are not constrained to be equal. We incorporated a megapixel silicon double-sided strip detector to permit ultrahigh-resolution imaging. We describe the configuration of the adjustable slit aperture imaging system and discuss its application toward adaptive imaging, and reconstruction techniques using an accurate imaging forward model, a novel geometric calibration technique, and a GPU-based ultra-high-resolution reconstruction code.

The role of SPECT imaging of the dopaminergic system in translational research on Parkinson's disease

Imaging of the dopaminergic system with single photon emission computed tomography (SPECT), and particularly of the dopamine transporter (DAT) located in the striatum, is a well accepted tool in clinical practice to confirm or exclude loss of nigrostriatal dopamine (DA) neurons in patients suspected to suffer from Parkinson's disease (PD). SPECT techniques were developed successfully to image neurotransmitter systems, including the presynaptic DAT and postsynaptic dopamine D2/3 receptors, in rat and mouse models of PD. Here we review the results of preclinical SPECT studies of the dopaminergic system in rat and mouse models of PD. Initially, SPECT studies in animal models of PD were performed to validate that micro-SPECT is able to accurately assess parts of the dopaminergic system in small animals in-vivo. However, more recently, micro-SPECT DAT is increasingly used as a research tool to support the interpretation of human DAT SPECT studies in PD, including clinical trials examining the effects of potential neuroprotective drugs. Translational research with SPECT is an interesting development which may further increase our understanding of the pathophysiology and treatment of PD.