Peter L. Kench

Small animal SPECT and its place in the matrix of molecular imaging technologies

Molecular imaging refers to the use of non-invasive imaging techniques to detect signals that originate from molecules, often in the form of an injected tracer, and observe their interaction with a specific cellular target in vivo. Differences in the underlying physical principles of these measurement techniques determine the sensitivity, specificity and length of possible observation of the signal, characteristics that have to be traded off according to the biological question under study. Here, we describe the specific characteristics of single photon emission computed tomography (SPECT) relative to other molecular imaging technologies. SPECT is based on the tracer principle and external radiation detection. It is capable of measuring the biodistribution of minute (<10(-10) molar) concentrations of radio-labelled biomolecules in vivo with sub-millimetre resolution and quantifying the molecular kinetic processes in which they participate. Like some other imaging techniques, SPECT was originally developed for human use and was subsequently adapted for imaging small laboratory animals at high spatial resolution for basic and translational research. Its unique capabilities include (i) the ability to image endogenous ligands such as peptides and antibodies due to the relative ease of labelling these molecules with technetium or iodine, (ii) the ability to measure relatively slow kinetic processes (compared with positron emission tomography, for example) due to the long half-life of the commonly used isotopes and (iii) the ability to probe two or more molecular pathways simultaneously by detecting isotopes with different emission energies. In this paper, we review the technology developments and design tradeoffs that led to the current state-of-the-art in SPECT small animal scanning and describe the position SPECT occupies within the matrix of molecular imaging technologies.

Screening mammography: test set data can reasonably describe actual clinical reporting.

PURPOSE To establish the extent to which test set reading can represent actual clinical reporting in screening mammography. MATERIALS AND METHODS Institutional ethics approval was granted, and informed consent was obtained from each participating screen reader. The need for informed consent with respect to the use of patient materials was waived. Two hundred mammographic examinations were selected from examinations reported by 10 individual expert screen readers, resulting in 10 reader-specific test sets. Data generated from actual clinical reports were compared with three test set conditions: clinical test set reading with prior images, laboratory test set reading with prior images, and laboratory test set reading without prior images. A further set of five expert screen readers was asked to interpret a common set of images in two identical test set conditions to establish a baseline for intraobserver variability. Confidence scores (from 1 to 4) were assigned to the respective decisions made by readers. Region-of-interest (ROI) figures of merit (FOMs) and side-specific sensitivity and specificity were described for the actual clinical reporting of each reader-specific test set and were compared with those for the three test set conditions. Agreement between pairs of readings was performed by using the Kendall coefficient of concordance. RESULTS Moderate or acceptable levels of agreement were evident (W = 0.69-0.73, P < .01) when describing group performance between actual clinical reporting and test set conditions that were reasonably close to the established baseline (W = 0.77, P < .01) and were lowest when prior images were excluded. Higher median values for ROI FOMs were demonstrated for the test set conditions than for the actual clinical reporting values; this was possibly linked to changes in sensitivity. CONCLUSION Reasonable levels of agreement between actual clinical reporting and test set conditions can be achieved, although inflated sensitivity may be evident with test set conditions.

Assessing reader performance in radiology, an imperfect science: lessons from breast screening.

The purpose of this article is to review the limitations associated with current methods of assessing reader accuracy in mammography screening programmes. Clinical audit is commonly used as a quality-assurance tool to monitor the performance of screen readers; however, a number of the metrics employed, such as recall rate as a surrogate for specificity, do not always accurately measure the intended clinical feature. Alternatively, standardized screening test sets, which benefit from ease of application, immediacy of results, and quicker assessment of quality improvement plans, suffer from experimental confounders, thus questioning the relevance of these laboratory-type screening test sets to clinical performance. Four key factors that impact on the external validity of screening test sets were identified: the nature and extent of scrutiny of ones action, the artificiality of the environment, the over-simplification of responses, and prevalence of abnormality. The impact of these factors on radiological and other contexts is discussed, and although it is important to acknowledge the benefit of standardized screening test sets, issues relating to the relevance of test sets to clinical activities remain. The degree of correlation between performance based on real-life clinical audit and performances at screen read test sets must be better understood and specific causal agents for any lack of correlation identified.

Performance evaluation of a multipinhole small animal SPECT system

We have designed and constructed a small animal SPECT system based on compact, high resolution detectors and multipinhole apertures. The scanner is currently configured with two detectors mounted on a rotating gantry. Each detector comprises a NaI(Tl) crystal array (1/spl times/1/spl times/5 mm elements), a 12 cm diameter position-sensitive photomultiplier tube (Hamamatsu R3292) and a tungsten aperture with 1 or more pinholes. In this study, we performed phantom experiments to characterise the planar and tomographic performance of the scanner. Intrinsic resolution measured with a highly collimated /sup 99m/Tc point source stepped across the detector face was 1.0 /spl plusmn/ 0;.1 FWHM and 2.9 /spl plusmn/ 0.1 mm FWTM. Energy resolution at 140 keV varied from 14% FWIIM for central crystals to 19% for edge crystals and was 20% FWHM for the whole detector normalised spectrum. Intrinsic uniformity for the central field of view was 2.4% differential and 3.8% integral. Reconstructed spatial resolution was 1.2 mm FWHM at the centre of the field of view and 1.2, 1.7 mm FWHM (radial, tangential) at 10 mm off-axis, using typical geometric parameters for mouse and rat brain imaging. Reconstructed images of a micro deluxe hot rod phantom demonstrate the high resolution of the system and indicate similar resolution and improved signal-to-noise is obtained with a 2 pinhole aperture compared with a single pinhole. We conclude that the performance characteristics of this system make it suitable for high resolution imaging of small laboratory animals.

Projection Process Modelling for Iterative Reconstruction of Pinhole SPECT

In iterative reconstruction of pinhole SPECT data, the forward and back projection processes are often performed using the ray tracing method. Ray tracing is computationally efficient, but it has the drawback of poor reconstruction quality due to the missing voxel effect and textural artefacts. In this paper, the pinhole projection process was modelled starting from consideration of all the main factors affecting pinhole projection, such as voxel shape, penetration of the pinhole edges and detector response. Next, approximations were made to reduce the computational speed and the effect of the approximations on reconstructed image accuracy was evaluated in simulation and phantom experiments and compared with the ray tracing algorithm. When used in conjunction with the ML-EM algorithm, the proposed model improved reconstructed image accuracy compared with the ray tracing method and achieved comparable computational efficiency. Therefore, the proposed projection model is a practical alternative to the ray tracing algorithm for pinhole SPECT reconstruction.

CoALA-SPECT: a coded aperture laboratory animal SPECT system for pre clinical imaging

We have previously demonstrated the potential of multi-pinhole coded apertures when used in conjunction with compact pixelated detectors for high resolution, high sensitivity small animal SPECT. We are now constructing a prototype SPECT system with three such detectors mounted on a rotating gantry. Each detector comprises a 12 cm diameter circular array of NaI(Tl) crystals, each 1/spl times/1/spl times/5 mm/sup 3/ on a 1.25 mm pitch. Each crystal array is coupled to a Hamamatsu R3292 12.7 cm diameter PS-PMT. Signals from the three detectors are read out by a custom subtractive resistive circuit and multiplexed. Data are acquired by a National Instruments PCI-6110E board running on a Macintosh dual processor G4 computer under Kmax software control. Images are reconstructed using a 3D iterative MAP-EM algorithm based on a multi-pinhole forward and back projector. The trade-off between contrast and variance was studied by simulation for a number of multi-pinhole configurations. We also performed initial planar imaging studies on one of the detectors. Our results indicate that spatial resolution approaching 1 mm full width at half maximum (FWHM) can be achieved with a single pinhole aperture, while improved contrast and variance may result from using optimized multi-pinhole apertures.

Strict X-ray beam collimation for facial bones examination can increase lens exposure

OBJECTIVES It is well accepted that collimation is a cost-effective dose-reducing tool for X-ray examinations. This phantom-based study investigated the impact of X-ray beam collimation on radiation dose to the lenses of the eyes and thyroid along with the effect on image quality in facial bone radiography. METHODS A three-view series (occipitomental, occipitomental 30 and lateral) was investigated, and radiation doses to the lenses and thyroid were measured using an Unfors dosemeter. Images were assessed by six experienced observers using a visual grading analysis and a total of 5400 observations were made. RESULTS Strict collimation significantly (p<0.0001) reduced the radiation dose to the lenses of the eyes and thyroid when using a fixed projection-specific exposure. With a variable exposure technique (fixed exit dose, to simulate the behaviour of an automatic exposure control), while strict collimation was again shown to reduce thyroid dose, higher lens doses were demonstrated when compared with larger fields of exposure. Image quality was found to significantly improve using strict collimation, with observer preference being demonstrated using visual grading characteristic curves. CONCLUSION The complexities of optimising radiographic techniques have been shown and the data presented emphasise the importance of examining dose-reducing strategies in a comprehensive way.

High-resolution imaging of the large non-human primate brain using microPET: a feasibility study

The neuroanatomy and physiology of the baboon brain closely resembles that of the human brain and is well suited for evaluating promising new radioligands in non-human primates by PET and SPECT prior to their use in humans. These studies are commonly performed on clinical scanners with 5 mm spatial resolution at best, resulting in sub-optimal images for quantitative analysis. This study assessed the feasibility of using a microPET animal scanner to image the brains of large non-human primates, i.e. papio hamadryas (baboon) at high resolution. Factors affecting image accuracy, including scatter, attenuation and spatial resolution, were measured under conditions approximating a baboon brain and using different reconstruction strategies. Scatter fraction measured 32% at the centre of a 10 cm diameter phantom. Scatter correction increased image contrast by up to 21% but reduced the signal-to-noise ratio. Volume resolution was superior and more uniform using maximum a posteriori (MAP) reconstructed images (3.2-3.6 mm(3) FWHM from centre to 4 cm offset) compared to both 3D ordered subsets expectation maximization (OSEM) (5.6-8.3 mm(3)) and 3D reprojection (3DRP) (5.9-9.1 mm(3)). A pilot (18)F-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) scan was performed on a healthy female adult baboon. The pilot study demonstrated the ability to adequately resolve cortical and sub-cortical grey matter structures in the baboon brain and improved contrast when images were corrected for attenuation and scatter and reconstructed by MAP. We conclude that high resolution imaging of the baboon brain with microPET is feasible with appropriate choices of reconstruction strategy and corrections for degrading physical effects. Further work to develop suitable correction algorithms for high-resolution large primate imaging is warranted.

Radiation dose and diagnostic image quality associated with iterative reconstruction in coronary CT angiography: A systematic review

The aim of this systematic review is to evaluate the radiation dose reduction achieved using iterative reconstruction (IR) compared to filtered back projection (FBP) in coronary CT angiography (CCTA) and assess the impact on diagnostic image quality. A systematic search of seven electronic databases was performed to identify all studies using a developed keywords strategy. A total of 14 studies met the criteria and were included in a review analysis. The results showed that there was a significant reduction in radiation dose when using IR compared to FBP (P < 0.05). The mean and standard deviation (SD) difference of CTDIvol and dose‐length‐product (DLP) were 14.70 ± 6.87 mGy and 186 ± 120 mGy.cm respectively. The mean ± SD difference of effective dose (ED) was 2.9 ± 1.7 mSv with the range from 1.0 to 5.0 mSv. The assessment of diagnostic image quality showed no significant difference (P > 0.05). The mean ± SD difference of image noise, signal‐noise ratio (SNR) and contrast‐noise ratio (CNR) were 1.05 ± 1.29 HU, 0.88 ± 0.56 and 0.63 ± 1.83 respectively. The mean ± SD percentages of overall image quality scores were 71.79 ± 12.29% (FBP) and 67.31 ± 22.96% (IR). The mean ± SD percentages of coronary segment analysis were 95.43 ± 2.57% (FBP) and 97.19 ± 2.62% (IR). In conclusion, this review analysis shows that CCTA with the use of IR leads to a significant reduction in radiation dose as compared to the use of FBP. Diagnostic image quality of IR at reduced dose (30–41%) is comparable to FBP at standard dose in the diagnosis of CAD.

DIAGNOSTIC REFERENCE LEVELS IN CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAPHY: A SYSTEMATIC REVIEW

Cardiac computed tomography angiography (CCTA) is a commonly used diagnostic tool for cardiovascular disease. Despite constant improvements to imaging technologies, the radiation dose to patients from CCTA remains a concern when using this procedure. There remains a need for optimisation of CCTA procedures and accurate dose monitoring to reduce the potential risk of cancer. Establishing diagnostic reference levels (DRLs) allows for the assessment of radiation dose variations, enabling strategies aimed at standardising doses across radiological centres. This systematic review explores the literature on CCTA methodologies that have been used to establish DRLs. A search was carried out using the Web of Science, SCOPUS, Medline, CINAHL and EMBASE databases. Reference lists of published articles were also assessed to identify further articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was employed to evaluate articles for relevance. Articles were included if they assessed DRLs in CCTA. The search resulted in 448 articles, of which, six were included after a thorough screening process. The literature demonstrates a wide dose variation in reported CCTA DRLs ranging from 671 to 1510 mGy cm in DLP. Where reported, CTDIvol DRLs ranged from 26 to 70 mGy. Differences were found in the methodologies used for establishing CCTA DRLs, including the sampling methodology used for identifying suitable patients and scanning protocols. This current review emphasises the need for an international standardisation for DRLs establishment methods, to provide a more comparable global measurement of dose variations across CT sites.