III.C.2 Spatial resolution
We have designed and built three Derenzo-like phantoms made of plexiglass to determine spatial resolution capabilities for the different FOVs considered (§II.B). The first one is a 20x20x5 mm 3 phantom with capillary tubes 3mm in length (open on the upper surface) drilled in it (Fig. 4a). A second one was designed for the determination of the transaxial spatial resolution. It consists of a cylinder with Derenzo-like geometry placed inside a holder cylinder 20 mm in diameter and 30 mm in length (Fig. 4b). The two above phantoms were used for spatial resolution determination of FOV20 and FOV40. Due to the dimensions of phantom in Fig. 4a), it can not be placed at vertical position because the cameras would crash with it during their rotation motion. For that reason it can be used only for axial spatial resolution determination. Moreover, as the spatial resolution for the FOV60 and FOV80 are worse than those for FOV20 and FOV40, we need the capillaries to be bigger (both in diameter and in center-to-center distances) than those used for the FOV20 and FOV40. For that reason we use for FOV 40 and FOV 80 the phantom in Fig. 4c). This phantom consists of a 40x40x4.5 mm 3 orthoedro with Derenzo-like geometry, placed inside a 40x40x9.5 mm 3 holder (Fig. 4c). In all cases the center-to-center distance between holes is twice the hole diameter. Total acquisition time was 45 min using 50 MBq of a 99m Tc solution. The images were reconstructed using the 3D- OSEM algorithm and 5 iterations (5 subsets for the single- pinhole, except for FOV20 where 15 subsets were considered, and 15 subsets for the multi-pinhole data). These parameters (number of subsets and number of iterations) were optimised for single-pinhole and multi-pinhole configurations as a balance among the image quality (both spatial resolution and noise), time required for image reconstruction, and system matrix size.
The LabPET™-8 is the PET subsystem of the integrated trimodality Triumph TM PET/SPECT/CT pre-clinical imaging sys- tem (Gamma Medica, Inc., Northridge, CA). It is a state-of-art avalanche photodiode (APD)-based digital small-animalPET scanner designed with quasi-individual crystal readout along with parallel digital architecture to achieve high performance [ 24 ]. The scanner has 7.5-cm axial and 10-cm transaxial FOVs. Scintillators of 2×2×12/14 mm 3 in size are composed of a Lu0.4Gd1.6SiO5 (LGSO) and Lu 1.9 Y 0.1 SiO 5 (LYSO). These are optically coupled one after the other, forming phoswich pairs of detectors. Four phoswich detectors are enclosed in a hermetic container made of kovar (an alloy of iron–nickel–cobalt having a density of 8.359 g/ cm 3 ). The end of the axial FOV shielding is made of tungsten (19.3 g/cm 3 density, 15.75 mm thickness and 131 mm internal diameter) to minimize the detection of out-of-FOV activity. The most relevant design features of the LabPET™-8 can be found in [ 24 ], whereas the technical speciﬁcations and performance assess-
Diffuse optical tomography (DOT), is a non-invasive imaging technique in which near-infrared light is used to probe the interior of the brain to record oxygenation and other physiological changes, which may have occurred after a stroke, seizure or haemorrhage. Although the spatial resolution is limited compared to MRI, the advantage of DOT is its simplicity and speed of measurements; the instruments are compact and portable, about the size of a small suitcase and a laptop, and can therefore, easily be taken to the bedside for constant monitoring of brain activity. The DOT analysis involves spectroscopy to monitor haemoglobin involved in oxygenation and therefore, this system also enables the identification of other metabolites such as proteins. Applications include diagnostic imaging of joints and limbs and mammography.
The data were reconstructed in the system's dedicated reconstruction program with an iterative reconstruction algorithm, resulting in a voxel size of 0.3 mm. After image reconstruction, the images were straightened and analyzed using InVivoScope software (Bioscan Inc.). Straightening of the images was assisted by the CT images. To avoid the variability of the slice selection and to gain statistical power, we used the entire striatum vol- ume for the analysis. Time-activity curves were obtained from the kinetics data by manually delineating the volumes of interest (VOIs). At each time point, the VOIs were drawn over specific (striatal) and nonspecific (cere- bellar) brain structures, and the mean counts in these two areas were measured against time. From the mean values obtained, we calculated the BP, which represents the ratio of the distribution volumes of the specifically and the nonspecifically bound compartment.
Ultrasound (US) and computed tomography (CT) are the most widely used imaging techniques for liver me- tastasis. However, these modalities are not able to meas- ure or detect altered functional features of the liver. CT and US detect only the presence of tumorous cells with acceptable sensitivity in a size range above 10 mm. In these cases, the liver function has already been affected and multiple small metastases could be present, too. Further quantitative and functional diagnostics of malig- nant alterations include positron emission tomography (PET) [2, 3] and dynamic contrast-enhanced magnetic resonance imaging (MRI)  with gadoxetic acid  or gadoxetate disodium [6, 7]. Several radiotracers have been investigated for single-photon emission computed tomography (SPECT) that is able to measure the liver function in different ways [2, 3, 5, 8, 9].
Mike Casey and Ronald Nutt , from CTI, introduce the "Block“ detector that was conceived as a means to simplify the Burnham detector and to make it easier to manufacture. Almost all dedicated tomographs built since 1985 have used some forms of the Block detector. This invention has made possible high-resolution PET tomographs at a much-reduced cost.
Chapter 4: Spatial Resolution Recovery algorithm 4.1 Introduction
Spatial resolution is the ability of an imaging device to provide a sharp (detailed) image. In nuclear medicine, a number factors contribute to the loss of image sharpness, such as collimator resolution, intrinsic resolution and patient movement. In gamma cameras with absorptive collimators, the major limiting factor of image resolution is the collimator resolution. In PET though, the intrinsic resolution of the detectors, i.e. the size of individual detector elements, limit the image resolution. Collimator resolution depends on the diameters of the holes and the source- to-detector distance, which contribute to image blurring. Patient movement, such respiration and cardiac motion, can be troublesome when imaging is performed for a longer period, but which can be corrected by using gated-imaging techniques to minimize motion blurring. Spatial resolution in SPECT is characterized using the profile of the reconstructed image of a line source or point source, usually a 99m Tc point source, placed in the field of view (FOV) of the camera. The profile through the center image of the point source gives the point spread function (PSF). Spatial resolution is then characterized by the full width at half maximum (FWHM) of the PSF. The intrinsic spatial resolution of PET is a Gaussian function with FWHM that changes with the location of the source from the two detectors, highest at the face of either detector.
department. If the animals from the C-corridor will be transported back from LBIC facility, consult with Lena Persson Feld for further instructions.
• All transport of animal cages must be done in cabinets that are ventilated or have a filter top. This also applies to empty used cages, which must be placed on the unclean side of the dishwashing room, in the specially appointed place.
Regulation of temperature and oxygen are critical to a well- executed study. These key factors can affect the physiology of your animal, and therefore your data. Simply glide the Imaging Chamber into the Docking Station to automatically deliver heat and anesthesia.
In 31 cases, the degree of uptake was mild according to the criteria adopted in the study (i.e., lower than the degree of uptake in the liver and higher than the degree of uptake in soft tissues). In eight cases, the degree of uptake was similar to the degree of liver uptake and was therefore considered moderate. Although the degree of uptake was considered mild for most lesions, it was much higher than the degree of uptake seen in soft tissues. It is possible that the comparison criteria that were selected in an attempt to make the interpretation more objective were not adequate because we observed that the degree of liver uptake was very similar to the degree of heart uptake, which can be considered intense in these two organs. In contrast to the findings reported with FDG-PET in lung cancer, our study did not show any direct correlation between the degree of sestamibi uptake in primary lesions and lymph nodes and the size and histology classification of tumors. That means, larger lesions or more agressive histology types of tumors were not associated with higher sestamibi uptake. One potential explanation is a difference in the transmembrane electrical potential, while another is the degree of neovas- cularity. Although aggressive histologies should show higher levels of sestamibi uptake, this phenomenon was not observed in our study sample. The size of the tumor is important because larger tumors are more easily detected by SPECTimaging. However, larger tumors have larger necrotic areas. In addition, necrotic, fibrotic and/or inflam- matory tissues were not quantified by the pathology examinations in our study, and no corrective measurements were taken according to the histology findings.
Recently, a number of innovative hardware combinations of SPECT and CT were proposed, giving rise to the idea of disease-specific SPECT/CTimaging. Gambhir et al.  and Buechel et al.  demonstrated the clinical feasibility and technological benefit of a CdZnTe (CZT)-based SPECTimaging for cardiac applications. While this system is not combined with CT, it illustrates a major leap in SPECT instrumentation that could potentially enter into a new combination of SPECT/CT. The main benefit of CZT over standard scintillator-based SPECT detectors is the much higher energy resolution, which can be explored for dual- isotope imaging. CZT detectors are compact and future CZT SPECT/CT could be more physically integrated. However, today, production costs still limit the wider distribution of these novel SPECTimaging systems.
Quantitative Image Analysis
Reconstructed PET images were analyzed using the quAntitative onCology moleCUlar Analysis suiTE (ACCURATE), version v03012019 (13). Two semiautomated tumor delineation methods were used to seg- ment and analyze individual lesions per image (with a maximum of the 10 hottest lesions). The first semiautomated method was based on a fixed SUV threshold of 4.0 g/mL (SUV 5 4), whereas the other method, the so-called majority vote (MV2), was based on agreement in tumor de- lineation between multiple semiautomated methods (14). For clarity, an illustrative clinical image example and a schematic overview of the MV2 method are shown in Supplemental Figures 1 and 2, respectively. If the semiautomated methods were incapable of delineating the lesion, then a 1-mL spheric volume of interest (VOI) was manually placed on (the hottest part in) the lesion. Analyses were performed using SUV max and
While image fusion techniques have been in clinical use for many years, the first commercial SPECT/CTsystem was only introduced in 1999. This system combined a low-power X ray tube with separate gamma and X ray detectors mounted on the same slip ring gantry. The X ray system operated at 140 kV with a tube current of only 2.5 mA. This resulted in a significantly lower patient dose than that received during a conventional CTimaging procedure (by a factor of 4–5), but the quality of the CT images was inferior to state of the art CT. Nevertheless, the fan beam formed by the X ray tube on the detectors allowed the measurement of patient attenuation along discrete paths providing significantly higher quality attenuation maps than those available with conventional 153 Gd scanning lines sources [1, 2]. This system has recently been equipped with a 4 slice low-dose CT scanner yielding an axial slice thickness of 5 mm with each rotation instead of one 10 mm slice. This tool retains the very compact design of the previous system, delivers a low radiation dose to the patient and requires minimal room shielding [2, 3]. Over the last 2–3 years there has been a large expansion of SPECT/CT technology worldwide and, as at June 2007, there are approximately 600 of these installations around the world and over 200 across the United States. The relatively large distribution of these SPECT/CT systems equipped with a low definition CT tube versus those equipped with high definition, standard diagnostic CT tubes (see below) can be explained by two main factors: 1) this is the first SPECT/CTsystem made commercially available, and 2) the overall cost of these tomographs (equipped with a low definition CT component) is considerably lower than that of tomographs equipped with a CT component having full diagnostic capabilities.
Quantitative image analysis was performed using the VivoQuant TM (inviCRO, Boston, MA, USA) analysis soft- ware. To derive dynamic radioactivity concentrations in various thoracic tissues, the following volumes of interest (VOIs) were defined on the multi-frame SPECT dataset: three-dimensional segmentations of the left ventricular (LV) myocardium and liver parenchyma were automatic- ally defined on the SPECT images using Otsu threshold- ing [20,21], subsequently controlled and manually adjusted if needed (e.g., in the inferior wall of the left ven- tricle, where the liver spillover can be considerable). A standardized blood pool volume of interest (VOI) (0.55 mm 3 ) was manually placed in the center of the lumen of the left ventricle. Lung VOIs were derived using thresh- olding on the reconstructed CT images, and projected onto the SPECT images. Normalized uptake values were calculated from each VOI for each time frame as radio- activity concentration (bequerels per milliliter) corrected for the injected dose per gram body weight (grams per milliliter).
Case presentation: A 69-year old, male patient with moderate pain in his posterior pelvic region was diagnosed with an unclear tumor of the iliac bone. Conventional radiographs, computed tomography (CT), and MRI imaging were inconclusive to confirm or refute a malignant process. There was no abnormal hyperperfusion on the early images. On the delayed images, moderately increased osteoblastic activity was noted, and the provisional diagnosis was in favor of a benign process.
The nuclear medicine departments and, in general, the aforementioned reference structures take into account the publications of the International Commission on Radiological Protection (ICRP) on the biological effects of radiation, NRDs, as well as dosimetric problems for patients and medical personnel. . The activity to be administered is, in general terms, a compromise between the quality of the image and the radiation exposure of the patient and the staff. The higher the activity administered, the better the quality of the image and the higher the radiation exposure of the patient and staff. The activity to be administered depends on the type of equipment (single or multiple head scintillation camera, or camera based on a CZT detector), patient characteristics (body weight), acquisition protocol (protocols of one or two days, imaging time, pixel size, controlled acquisition) and the radiopharmaceutical. The reconstruction method may also be important, that is to say a filtered backprojection compared to an iterative reconstruction. The three key principles of radiation protection are justification, optimization and dose limitation. The dose limits and dose constraints of the ICRP are not recommended individually for a patient, as they can reduce the effectiveness of the diagnosis or treatment of the patient, thus doing more harm than good.
Tc-sestaMIBI dual-phase and 99m Tc-sestaMIBI SPECT/CT images. Visual examination was performed to search for sites with higher focal tracer uptake in PET and SPECT images than the adjacent background activ- ity and with a corresponding nodular lesion on CT. The size, maximum standard uptake value (SUVmax), and metabolic tumor volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax ) of the positive lesions were measured and used for semi-quantitative estimation. Lesions were localized anatomically to six regions: right upper, right lower, left upper, left lower thyroid, intrathyroidal, and ectopic (e.g., mediastinal).
A further interesting example of multi-modality imaging is represented by the paper of Kamson et al. , that evaluated the accuracy of α-[ 11 C]methyl- L -tryptophan (AMT)-positron
emission tomography (PET) to differentiate newly diagnosed glioblastomas and brain metastases in 36 adults with suspected brain malignancy. AMT is an amino acid positron-emitting promising radiopharmaceutical tracer able to measure tryptophan metabolism via the immunomodulatory kynurenine pathway [43 ]. Although this tracer is promising it is scarcely used because it is not widely available. Recent studies demonstrated that AMT accumulates for both transport and metabolism in untreated and recurrent gliomas [43,44]. Kamson et al.  measured tumour AMT accumulation by SUVs and radiopharmaceutical kinetic analysis was carried out to separate tumoral net tryptophan transport [by AMT volume of distribution (VD)] from unidirectional uptake rates by means of dynamic PET and blood input function. The differential accuracy of these PET variables was investigated and compared with conventional MRI. For glioblastoma/metastasis differentiation, tumoral AMT SUV presented the highest accuracy (74%) and the tumor/cortex VD ratio disclosed the highest positive predictive value (82%); the combined accuracy of MRI (providing size of contrast-enhancing lesion) and AMT-PET was up to 93%. For ring-enhancing lesions, tumour/cortex SUV ratios were higher in glioblastomas comparing with metastatic tumours and were capable to differentiate these two tumour types with great accuracy (higher than 90%). These findings demonstrated that AMT PET can contribute to enhance pretreatment differentiation of glioblastomas and metastatic brain tumors and it may be particularly useful in patients with a newly diagnosed solitary ring-enhancing mass detected by MRI.