Creation of an anthropomorphic CT head phantom for verification of image segmentation.

PURPOSE: Many methods are available to segment structural magnetic resonance (MR) images of the brain into different tissue types. These have generally been developed for research purposes but there is some clinical use in the diagnosis of neurodegenerative diseases such as dementia. The potential exists for computed tomography (CT) segmentation to be used in place of MRI segmentation, but this will require a method to verify the accuracy of CT processing, particularly if algorithms developed for MR are used, as MR has notably greater tissue contrast. METHODS: To investigate these issues we have created a three-dimensional (3D) printed brain with realistic Hounsfield unit (HU) values based on tissue maps segmented directly from an individual T1 MRI scan of a normal subject. Several T1 MRI scans of normal subjects from the ADNI database were segmented using SPM12 and used to create stereolithography files of different tissues for 3D printing. The attenuation properties of several material blends were investigated, and three suitable formulations were used to print an object expected to have realistic geometry and attenuation properties. A skull was simulated by coating the object with plaster of Paris impregnated bandages. Using two CT scanners, the realism of the phantom was assessed by the measurement of HU values, SPM12 segmentation and comparison with the source data used to create the phantom. RESULTS: Realistic relative HU values were measured although a subtraction of 60 was required to obtain equivalence with the expected values (gray matter 32.9-35.8 phantom, 29.9-34.2 literature). Segmentation of images acquired at different kVps/mAs showed excellent agreement with the source data (Dice Similarity Coefficient 0.79 for gray matter). The performance of two scanners with two segmentation methods was compared, with the scanners found to have similar performance and with one segmentation method clearly superior to the other. CONCLUSION: The ability to use 3D printing to create a realistic (in terms of geometry and attenuation properties) head phantom has been demonstrated and used in an initial assessment of CT segmentation accuracy using freely available software developed for MRI.

Technical Note: Development of a 3D printed subresolution sandwich phantom for validation of brain SPECT analysis.

PURPOSE: To make an adaptable, head shaped radionuclide phantom to simulate molecular imaging of the brain using clinical acquisition and reconstruction protocols. This will allow the characterization and correction of scanner characteristics, and improve the accuracy of clinical image analysis, including the application of databases of normal subjects. METHODS: A fused deposition modeling 3D printer was used to create a head shaped phantom made up of transaxial slabs, derived from a simulated MRI dataset. The attenuation of the printed polylactide (PLA), measured by means of the Hounsfield unit on CT scanning, was set to match that of the brain by adjusting the proportion of plastic filament and air (fill ratio). Transmission measurements were made to verify the attenuation of the printed slabs. The radionuclide distribution within the phantom was created by adding (99m)Tc pertechnetate to the ink cartridge of a paper printer and printing images of gray and white matter anatomy, segmented from the same MRI data. The complete subresolution sandwich phantom was assembled from alternate 3D printed slabs and radioactive paper sheets, and then imaged on a dual headed gamma camera to simulate an HMPAO SPECT scan. RESULTS: Reconstructions of phantom scans successfully used automated ellipse fitting to apply attenuation correction. This removed the variability inherent in manual application of attenuation correction and registration inherent in existing cylindrical phantom designs. The resulting images were assessed visually and by count profiles and found to be similar to those from an existing elliptical PMMA phantom. CONCLUSIONS: The authors have demonstrated the ability to create physically realistic HMPAO SPECT simulations using a novel head-shaped 3D printed subresolution sandwich method phantom. The phantom can be used to validate all neurological SPECT imaging applications. A simple modification of the phantom design to use thinner slabs would make it suitable for use in PET.

Regional cerebral blood flow single photon emission computed tomography for detection of Frontotemporal dementia in people with suspected dementia.

BACKGROUND: In the UK, dementia affects 5% of the population aged over 65 years and 25% of those over 85 years. Frontotemporal dementia (FTD) represents one subtype and is thought to account for up to 16% of all degenerative dementias. Although the core of the diagnostic process in dementia rests firmly on clinical and cognitive assessments, a wide range of investigations are available to aid diagnosis.Regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) is an established clinical tool that uses an intravenously injected radiolabelled tracer to map blood flow in the brain. In FTD the characteristic pattern seen is hypoperfusion of the frontal and anterior temporal lobes. This pattern of blood flow is different to patterns seen in other subtypes of dementia and so can be used to differentiate FTD.It has been proposed that a diagnosis of FTD, (particularly early stage), should be made not only on the basis of clinical criteria but using a combination of other diagnostic findings, including rCBF SPECT. However, more extensive testing comes at a financial cost, and with a potential risk to patient safety and comfort. OBJECTIVES: To determine the diagnostic accuracy of rCBF SPECT for diagnosing FTD in populations with suspected dementia in secondary/tertiary healthcare settings and in the differential diagnosis of FTD from other dementia subtypes. SEARCH METHODS: Our search strategy used two concepts: (a) the index test and (b) the condition of interest. We searched citation databases, including MEDLINE (Ovid SP), EMBASE (Ovid SP), BIOSIS (Ovid SP), Web of Science Core Collection (ISI Web of Science), PsycINFO (Ovid SP), CINAHL (EBSCOhost) and LILACS (Bireme), using structured search strategies appropriate for each database. In addition we searched specialised sources of diagnostic test accuracy studies and reviews including: MEDION (Universities of Maastricht and Leuven), DARE (Database of Abstracts of Reviews of Effects) and HTA (Health Technology Assessment) database.We requested a search of the Cochrane Register of Diagnostic Test Accuracy Studies and used the related articles feature in PubMed to search for additional studies. We tracked key studies in citation databases such as Science Citation Index and Scopus to ascertain any further relevant studies. We identified 'grey' literature, mainly in the form of conference abstracts, through the Web of Science Core Collection, including Conference Proceedings Citation Index and Embase. The most recent search for this review was run on the 1 June 2013.Following title and abstract screening of the search results, full-text papers were obtained for each potentially eligible study. These papers were then independently evaluated for inclusion or exclusion. SELECTION CRITERIA: We included both case-control and cohort (delayed verification of diagnosis) studies. Where studies used a case-control design we included all participants who had a clinical diagnosis of FTD or other dementia subtype using standard clinical diagnostic criteria. For cohort studies, we included studies where all participants with suspected dementia were administered rCBF SPECT at baseline. We excluded studies of participants from selected populations (e.g. post-stroke) and studies of participants with a secondary cause of cognitive impairment. DATA COLLECTION AND ANALYSIS: Two review authors extracted information on study characteristics and data for the assessment of methodological quality and the investigation of heterogeneity. We assessed the methodological quality of each study using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. We produced a narrative summary describing numbers of studies that were found to have high/low/unclear risk of bias as well as concerns regarding applicability. To produce 2 x 2 tables, we dichotomised the rCBF SPECT results (scan positive or negative for FTD) and cross-tabulated them against the results for the reference standard. These tables were then used to calculate the sensitivity and specificity of the index test. Meta-analysis was not performed due to the considerable between-study variation in clinical and methodological characteristics. MAIN RESULTS: Eleven studies (1117 participants) met our inclusion criteria. These consisted of six case-control studies, two retrospective cohort studies and three prospective cohort studies. Three studies used single-headed camera SPECT while the remaining eight used multiple-headed camera SPECT. Study design and methods varied widely. Overall, participant selection was not well described and the studies were judged as having either high or unclear risk of bias. Often the threshold used to define a positive SPECT result was not predefined and the results were reported with knowledge of the reference standard. Concerns regarding applicability of the studies to the review question were generally low across all three domains (participant selection, index test and reference standard).Sensitivities and specificities for differentiating FTD from non-FTD ranged from 0.73 to 1.00 and from 0.80 to 1.00, respectively, for the three multiple-headed camera studies. Sensitivities were lower for the two single-headed camera studies; one reported a sensitivity and specificity of 0.40 (95% confidence interval (CI) 0.05 to 0.85) and 0.95 (95% CI 0.90 to 0.98), respectively, and the other a sensitivity and specificity of 0.36 (95% CI 0.24 to 0.50) and 0.92 (95% CI 0.88 to 0.95), respectively.Eight of the 11 studies which used SPECT to differentiate FTD from Alzheimer's disease used multiple-headed camera SPECT. Of these studies, five used a case-control design and reported sensitivities of between 0.52 and 1.00, and specificities of between 0.41 and 0.86. The remaining three studies used a cohort design and reported sensitivities of between 0.73 and 1.00, and specificities of between 0.94 and 1.00. The three studies that used single-headed camera SPECT reported sensitivities of between 0.40 and 0.80, and specificities of between 0.61 and 0.97. AUTHORS' CONCLUSIONS: At present, we would not recommend the routine use of rCBF SPECT in clinical practice because there is insufficient evidence from the available literature to support this.Further research into the use of rCBF SPECT for differentiating FTD from other dementias is required. In particular, protocols should be standardised, study populations should be well described, the threshold for 'abnormal' scans predefined and clear details given on how scans are analysed. More prospective cohort studies that verify the presence or absence of FTD during a period of follow up should be undertaken.

Generation of realistic HMPAO SPECT images using a subresolution sandwich phantom.

UNLABELLED: Traditional interpretation of rCBF SPECT data is of a qualitative nature and is dependent on the observer's understanding of the normal distribution of the tracer. The use of a normal database in quantitative regional analysis facilitates the detection of functional abnormality in individual and group studies by accounting for inter-subject variability. The ability to simulate realistic images would allow various important areas related to the use of normal databases to be studied. These include the optimisation of the detection of abnormal blood flow and the portability of normal databases between gamma camera systems. To investigate this further we have constructed a hardware phantom and scanned various configurations of radioactive brain patterns and simulated skull configurations. METHODS: A subresolution sandwich phantom was constructed with a simulated skull which was assembled using a high-resolution segmented MR scan printed with a (99m)TcO4 - mixture and scanned using a double-headed gamma camera with parallel-hole collimators. Various different grey-to-white matter (GM:WM) ratios and aluminium simulated skull configurations were used. A single difference measure between the phantom data and a control database mean image was used for optimisation. The realism of phantom data was assessed using statistical parametric mapping (SPM) and ROI analysis. RESULTS: Optimisation was achieved with a range of WM:GM ratios from 1.9 to 2.4:1 with various simulated skull configurations. CONCLUSION: The ability to simulate realistic HMPAO SPECT scans has been demonstrated using a subresolution sandwich phantom. Further work, involving scanning the optimised phantom on different gamma camera systems and comparison with camera-specific normal databases should further refine the phantom configuration.

The contribution of statistical parametric mapping in the assessment of precuneal and medial temporal lobe perfusion by 99mTc-HMPAO SPECT in mild Alzheimer's and Lewy body dementia.

AIM: To assess the role of 99mTc-hexamethylpropyleneamine oxime single-photon emission computed tomography (99mTc-HMPAO SPECT) imaging of the precuneus and medial temporal lobe in the individual patient with mild Alzheimer's disease and dementia with Lewy bodies (DLB) using statistical parametric mapping and visual image interpretation. METHODS: Thirty-four patients with mild late-onset Alzheimer's disease, 20 patients with early-onset Alzheimer's disease, 15 patients with DLB and 31 healthy controls were studied. All patients fulfilled appropriate clinical criteria; the DLB patients also had evidence of dopaminergic presynaptic terminal loss on 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane imaging. 99mTc-HMPAO SPECT brain scans were acquired on a multidetector gamma camera and images were assessed separately by visual interpretation and with SPM99. RESULTS: Statistical parametric maps were significantly more accurate than visual image interpretation in all disease categories. In patients with mild late-onset Alzheimer's disease, statistical parametric mapping demonstrated significant hypoperfusion to the precuneus in 59% and to the medial temporal lobe in 53%. Seventy-six per cent of these patients had a defect in either location. No controls had precuneal or medial temporal lobe hypoperfusion (specificity, 100%). Statistical parametric mapping also demonstrated 73% of patients with DLB to have precuneal abnormalities, but only 6% had medial temporal lobe involvement. CONCLUSION: These findings illustrate the capability of statistical parametric mapping to demonstrate reliable abnormalities in the majority, but not all, patients with either mild Alzheimer's disease or DLB. Precuneal hypoperfusion is not specific to Alzheimer's disease and is equally likely to be found in DLB. In this study, medial temporal hypoperfusion was significantly more common in Alzheimer's disease than in DLB. Statistical parametric maps appear to be considerably more reliable than simple visual interpretation of 99mTc-HMPAO images for these regions.