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1.  Staging the axilla in breast cancer patients with 18F-FDG PET: how small are the metastases that we can detect with new generation clinical PET systems? 
Point spread function (PSF) reconstruction improves spatial resolution throughout the entire field of view of a PET system and can detect smaller metastatic deposits than conventional algorithms such as OSEM. We assessed the impact of PSF reconstruction on quantitative values and diagnostic accuracy for axillary staging of breast cancer patients, compared with an OSEM reconstruction, with emphasis on the size of nodal metastases.
This was a prospective study in a single referral centre in which 50 patients underwent an 18F-FDG PET examination before axillary lymph node dissection. PET data were reconstructed with an OSEM algorithm and PSF reconstruction, analysed blindly and validated by a pathologist who measured the largest nodal metastasis per axilla. This size was used to evaluate PET diagnostic performance.
On pathology, 34 patients (68 %) had nodal involvement. Overall, the median size of the largest nodal metastasis per axilla was 7 mm (range 0.5 – 40 mm). PSF reconstruction detected more involved nodes than OSEM reconstruction (p = 0.003). The mean PSF to OSEM SUVmax ratio was 1.66 (95 % CI 1.01 – 2.32). The sensitivities of PSF and OSEM reconstructions were, respectively, 96 % and 92 % in patients with a largest nodal metastasis of >7 mm, 60 % and 40 % in patients with a largest nodal metastasis of ≤7 mm, and 92 % and 69 % in patients with a primary tumour ≤30 mm. Biggerstaff graphical comparison showed that globally PSF reconstruction was superior to OSEM reconstruction. The median sizes of the largest nodal metastasis in patients with nodal involvement not detected by either PSF or OSEM reconstruction, detected by PSF but not by OSEM reconstruction and detected by both reconstructions were 3, 6 and 16 mm (p = 0.0064) respectively. In patients with nodal involvement detected by PSF reconstruction but not by OSEM reconstruction, the smallest detectable metastasis was 1.8 mm.
As a result of better activity recovery, PET with PSF reconstruction performed better than PET with OSEM reconstruction in detecting nodal metastases ≤7 mm. However, its sensitivity is still insufficient for it to replace surgical approaches for axillary staging. PET with PSF reconstruction could be used to perform sentinel node biopsy more safely in patients with a primary tumour ≤30 mm and with unremarkable PET results in the axilla.
Electronic supplementary material
The online version of this article (doi:10.1007/s00259-014-2689-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4006125  PMID: 24562642
PET/CT; Breast cancer; Axillary staging; Fluorodeoxyglucose; PSF reconstruction
2.  Effect of Varying Number of OSEM Subsets on PET Lesion Detectability 
Journal of nuclear medicine technology  2013;41(4):10.2967/jnmt.113.131904.
Iterative reconstruction has become the standard for routine clinical positron emission tomography (PET) imaging. However, iterative reconstruction is computationally expensive, especially for time-of-flight (TOF) data. Block-iterative algorithms such as ordered-subsets expectation-maximization (OSEM) are commonly used to accelerate the reconstruction. There is a tradeoff between the number of subsets and reconstructed image quality. The objective of this work was to evaluate the effect of varying the number of OSEM subsets upon lesion-detection for general oncologic PET imaging.
Experimental phantom data were taken from the Utah PET Lesion Detection Database resource, modeling whole-body oncologic PET imaging of a 92 Kg patient with [18]F-fluorodeoxyglucose. The experiment consisted of 24 scans over 4 days on a TOF PET/CT scanner, with up to 23 lesions (diameter 6–16mm) distributed throughout the thorax, abdomen, and pelvis. Images were reconstructed with maximum-likelihood expectation-maximization (MLEM) and with OSEM using 2–84 subsets. The reconstructions were repeated both with and without TOF. Localization receiver operating characteristics (LROC) analysis was applied using the channelized non-prewhitened observer. The observer was first used to optimize the number of iterations and smoothing filter for each case that maximized lesion-detection performance for these data; this was done to ensure that fair comparisons were made with each test case operating near its optimal performance. The probability of correct localization (PLOC) and the area under the LROC curve (ALROC) were then analyzed as functions of the number of subsets to characterize the effect of OSEM on lesion-detection performance.
Compared to the baseline MLEM algorithm, lesion-detection performance with OSEM declined as the number of subsets increased. The decline was moderate out to about 12–14 subsets, and then became progressively steeper as the number of subsets increased. Comparing TOF with non-TOF results, the magnitude of the performance drop was larger for TOF reconstructions.
PET lesion-detection performance is degraded when using OSEM with a large number of subsets. This loss of image quality can be controlled by using a moderate number of subsets (e.g. 12–14 or fewer), retaining a large degree of acceleration while maintaining high image quality. The use of more aggressive subsetting can result in image quality degradations that offset the benefits of using TOF or longer scan times.
PMCID: PMC3856855  PMID: 24221921
positron emission tomography (PET); OSEM; lesion-detection; observer study; LROC
3.  LOR-OSEM: statistical PET reconstruction from raw line-of-response histograms 
Physics in medicine and biology  2004;49(20):4731-4744.
Iterative statistical reconstruction methods are becoming the standard in positron emission tomography (PET). Conventional maximum-likelihood expectation-maximization (MLEM) and ordered-subsets (OSEM) algorithms act on data which has been pre-processed into corrected, evenly-spaced histograms; however, such pre-processing corrupts the Poisson statistics. Recent advances have incorporated attenuation, scatter, and randoms compensation into the iterative reconstruction. The objective of this work was to incorporate the remaining preprocessing steps, including arc correction, to reconstruct directly from raw unevenly-spaced line-of-response (LOR) histograms. This exactly preserves Poisson statistics and full spatial information in a manner closely related to listmode ML, making full use of the ML statistical model. The LOR-OSEM algorithm was implemented using a rotation-based projector which maps directly to the unevenly-spaced LOR grid. Simulation and phantom experiments were performed to characterize resolution, contrast, and noise properties for 2D PET. LOR-OSEM provided a beneficial noise-resolution tradeoff, outperforming AW-OSEM by about the same margin that AW-OSEM outperformed pre-corrected OSEM. The relationship between LOR-ML and listmode ML algorithms was explored, and implementation differences are discussed. LOR-OSEM is a viable alternative to AW-OSEM for histogram-based reconstruction with improved spatial resolution and noise properties.
PMCID: PMC2903972  PMID: 15566171
4.  Experimental Comparison of Lesion Detectability for Four Fully-3D PET Reconstruction Schemes 
The objective of this work was to evaluate the lesion detection performance of four fully-3D positron emission tomography (PET) reconstruction schemes using experimentally acquired data. A multi-compartment anthropomorphic phantom was set up to mimic whole-body 18F-fluorodeoxyglucose (FDG) cancer imaging and scanned 12 times in 3D mode, obtaining count levels typical of noisy clinical scans. Eight of the scans had 26 68Ge “shell-less” lesions (6, 8-, 10-, 12-, 16-mm diameter) placed throughout the phantom with various target:background ratios. This provided lesion-present and lesion-absent datasets with known truth appropriate for evaluating lesion detectability by localization receiver operating characteristic (LROC) methods. Four reconstruction schemes were studied: 1) Fourier rebinning (FORE) followed by 2D attenuation-weighted ordered-subsets expectation-maximization, 2) fully-3D AW-OSEM, 3) fully-3D ordinary-Poisson line-of-response (LOR-)OSEM; and 4) fully-3D LOR-OSEM with an accurate point-spread function (PSF) model. Two forms of LROC analysis were performed. First, a channelized nonprewhitened (CNPW) observer was used to optimize processing parameters (number of iterations, post-reconstruction filter) for the human observer study. Human observers then rated each image and selected the most-likely lesion location. The area under the LROC curve (ALROC) and the probability of correct localization were used as figures-of-merit. The results of the human observer study found no statistically significant difference between FORE and AW-OSEM3D (ALROC = 0.41 and 0.36, respectively), an increase in lesion detection performance for LOR-OSEM3D (ALROC = 0.45, p = 0.076), and additional improvement with the use of the PSF model (ALROC = 0.55, p = 0.024). The numerical CNPW observer provided the same rankings among algorithms, but obtained different values of ALROC. These results show improved lesion detection performance for the reconstruction algorithms with more sophisticated statistical and imaging models as compared to the previous-generation algorithms.
PMCID: PMC2798572  PMID: 19272998
Fully-3D PET; lesion detection; localization receiver operating characteristic (LROC); observer study; positron emission tomography (PET)
5.  Noise correlation in PET, CT, SPECT and PET/CT data evaluated using autocorrelation function: a phantom study on data, reconstructed using FBP and OSEM 
Positron Emission Tomography (PET), Computed Tomography (CT), PET/CT and Single Photon Emission Tomography (SPECT) are non-invasive imaging tools used for creating two dimensional (2D) cross section images of three dimensional (3D) objects. PET and SPECT have the potential of providing functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules, whereas CT visualizes X-ray density in tissues in the body. PET/CT provides fused images representing both functional and anatomical information with better precision in localization than PET alone.
Images generated by these types of techniques are generally noisy, thereby impairing the imaging potential and affecting the precision in quantitative values derived from the images. It is crucial to explore and understand the properties of noise in these imaging techniques. Here we used autocorrelation function (ACF) specifically to describe noise correlation and its non-isotropic behaviour in experimentally generated images of PET, CT, PET/CT and SPECT.
Experiments were performed using phantoms with different shapes. In PET and PET/CT studies, data were acquired in 2D acquisition mode and reconstructed by both analytical filter back projection (FBP) and iterative, ordered subsets expectation maximisation (OSEM) methods. In the PET/CT studies, different magnitudes of X-ray dose in the transmission were employed by using different mA settings for the X-ray tube. In the CT studies, data were acquired using different slice thickness with and without applied dose reduction function and the images were reconstructed by FBP. SPECT studies were performed in 2D, reconstructed using FBP and OSEM, using post 3D filtering. ACF images were generated from the primary images, and profiles across the ACF images were used to describe the noise correlation in different directions. The variance of noise across the images was visualised as images and with profiles across these images.
The most important finding was that the pattern of noise correlation is rotation symmetric or isotropic, independent of object shape in PET and PET/CT images reconstructed using the iterative method. This is, however, not the case in FBP images when the shape of phantom is not circular. Also CT images reconstructed using FBP show the same non-isotropic pattern independent of slice thickness and utilization of care dose function. SPECT images show an isotropic correlation of the noise independent of object shape or applied reconstruction algorithm. Noise in PET/CT images was identical independent of the applied X-ray dose in the transmission part (CT), indicating that the noise from transmission with the applied doses does not propagate into the PET images showing that the noise from the emission part is dominant. The results indicate that in human studies it is possible to utilize a low dose in transmission part while maintaining the noise behaviour and the quality of the images.
The combined effect of noise correlation for asymmetric objects and a varying noise variance across the image field significantly complicates the interpretation of the images when statistical methods are used, such as with statistical estimates of precision in average values, use of statistical parametric mapping methods and principal component analysis. Hence it is recommended that iterative reconstruction methods are used for such applications. However, it is possible to calculate the noise analytically in images reconstructed by FBP, while it is not possible to do the same calculation in images reconstructed by iterative methods. Therefore for performing statistical methods of analysis which depend on knowing the noise, FBP would be preferred.
PMCID: PMC1208889  PMID: 16122383
6.  Effect of Reconstruction Algorithms on Myocardial Blood Flow Measurement with 13N-Ammonia PET 
Filtered backprojection (FBP) is the traditional method for 13N-NH3 PET studies. Ordered-subsets expectation maximization (OSEM) is popular for PET studies because of better noise properties. Scant data exist on the effect of reconstruction algorithms on quantitative myocardial blood flow (MBF) estimation.
Twenty patients underwent dynamic acquisition rest/stress 13N-NH3 studies. In Part 1, 19 rest/stress image pairs were reconstructed by FBP (10-mm Hanning filter) and by OSEM with 28 subsets and 2 (OSEM2), 6 (OSEM6), or 8 iterations (OSEM8), and a 10-mm postreconstruction smoothing gaussian filter. In Part 2, 9 image pairs were reconstructed by FBP (10-mm Hanning filter) and by OSEM with 28 subsets, 8 iterations, and a gaussian 5-, 10-, or 15-mm postreconstruction smoothing filter. Average MBF (mL/min/mL of myocardium) was calculated using a 3-compartment model.
Part 1: For rest MBF, the correlations between FBP and each of the OSEM algorithms were r2 = 0.71, 0.73, and 0.77, respectively. MBF by OSEM6 (0.98 ± 0.48 [mean ± SD]) and OSEM8 (0.96 ± 0.46) was not significantly different from FBP (1.02 ± 0.39), but OSEM2 (0.80 ± 0.37) was significantly lower (P < 0.0003). With stress, the correlations were high between FBP and OSEM6 and OSEM8 (r2 = 0.85 and 0.90), and MBF by OSEM6 and OSEM8 was not significantly different from FBP. Part 2: Resting MBF correlated well between FBP and all OSEM smoothing filters (r2 = 0.82, 0.85, and 0.88). Rest MBF using postsmoothing 5- or 10-mm filters was not different from FBP but was significantly lower with the 15-mm filter (P < 0.05). With stress, the correlations were good between FBP and OSEM regardless of smoothing (r2 = 0.76, 0.77, and 0.79). However, MBF with postsmoothing 10- and 15-mm filters was significantly lower than by FBP (P < 0.05).
Reconstruction algorithms significantly affect the estimation of quantitative blood flow data and should not be assumed to be interchangeable. Although aggressive smoothing may produce visually appealing images with reduced noise levels, it may cause an underestimation of absolute quantitative MBF. In selecting a reconstruction algorithm, an optimal balance between noise properties and diagnostic accuracy must be emphasized.
PMCID: PMC2586832  PMID: 17631543
PET; reconstruction algorithms; myocardial blood flow
7.  Positron Emission Tomography for the Assessment of Myocardial Viability 
Executive Summary
The objective was to update the 2001 systematic review conducted by the Institute For Clinical Evaluative Sciences (ICES) on the use of positron emission tomography (PET) in assessing myocardial viability. The update consisted of a review and analysis of the research evidence published since the 2001 ICES review to determine the effectiveness and cost-effectiveness of PET in detecting left ventricular (LV) viability and predicting patient outcomes after revascularization in comparison with other noninvasive techniques.
Left Ventricular Viability
Heart failure is a complex syndrome that impairs the contractile ability of the heart to maintain adequate blood circulation, resulting in poor functional capacity and increased risk of morbidity and mortality. It is the leading cause of hospitalization in elderly Canadians. In more than two-thirds of cases, heart failure is secondary to coronary heart disease. It has been shown that dysfunctional myocardium resulting from coronary heart disease (CAD) may recover contractile function (i.e. considered viable). Dysfunctional but viable myocardium may have been stunned by a brief episode of ischemia, followed by restoration of perfusion, and may regain function spontaneously. It is believed that repetitive stunning results in hibernating myocardium that will only regain contractile function upon revascularization.
For people with CAD and severe LV dysfunction (left ventricular ejection fraction [LVEF] <35%) refractory to medical therapy, coronary artery bypass and heart transplantation are the only treatment options. The opportunity for a heart transplant is limited by scarcityof donor hearts. Coronary artery bypass in these patients is associated with high perioperative complications; however, there is evidence that revascularization in the presence of dysfunctional but viable myocardium is associated with survival benefits and lower rates of cardiac events. The assessment of left ventricular (LV) viability is, therefore, critical in deciding whether a patient with coronary artery disease and severe LV dysfunction should undergo revascularization, receive a heart transplant, or remain on medical therapy.
Assessment of Left Ventricular Viability
Techniques for assessing myocardial viability depend on the measurement of a specific characteristic of viable myocytes such as cell membrane integrity, preserved metabolism, mitochondria integrity, and preserved contractile reserve. In Ontario, single photon emission computed tomography (SPECT) using radioactive 201thallium is the most commonly used technique followed by dobutamine echocardiography. Newer techniques include SPECT using technetium tracers, cardiac magnetic resonance imaging, and PET, the subject of this review.
Positron Emission Tomography
PET is a nuclear imaging technique based on the metabolism of radioactive analogs of normal substrates such as glucose and water. The radiopharmaceutical used most frequently in myocardial viability assessment is F18 fluorodeoxyglucose (FDG), a glucose analog. The procedure involves the intravenous administration of FDG under controlled glycemic conditions, and imaging with a PET scanner. The images are reconstructed using computer software and analyzed visually or semi-quantitatively, often in conjunction with perfusion images. Dysfunctional but stunned myocardium is characterized by normal perfusion and normal FDG uptake; hibernating myocardium exhibits reduced perfusion and normal/enhanced FDG uptake (perfusion/metabolism mismatch), whereas scar tissue is characterized by reduction in both perfusion and FDG uptake (perfusion/metabolism match).
Review Strategy
The Medical Advisory Secretariat used a search strategy similar to that used in the 2001 ICES review to identify English language reports of health technology assessments and primary studies in selected databases, published from January 1, 2001 to April 20, 2005. Patients of interest were those with CAD and severe ventricular dysfunction being considered for revascularization that had undergone viability assessment using either PET and/or other noninvasive techniques. The outcomes of interest were diagnostic and predictive accuracy with respect to recovery of regional or global LV function, long-term survival and cardiac events, and quality of life. Other outcomes of interest were impact on treatment decision, adverse events, and cost-effectiveness ratios.
Of 456 citations, 8 systematic reviews/meta-analyses and 37 reports on primary studies met the selection criteria. The reports were categorized using the Medical Advisory Secretariat levels of evidence system, and the quality of the reports was assessed using the criteria of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) developed by the Centre for Dissemination of Research (National Health Service, United Kingdom). Analysis of sensitivity, specificity, predictive values and likelihood ratios were conducted for all data as well as stratified by mean left ventricular ejection fraction (LVEF). There were no randomized controlled trials. The included studies compared PET with one or more other noninvasive viability tests on the same group of patients or examined the long-term outcomes of PET viability assessments. The quality assessment showed that about 50% or more of the studies had selection bias, interpreted tests without blinding, excluded uninterpretable segments in the analysis, or did not have clearly stated selection criteria. Data from the above studies were integrated with data from the 2001 ICES review for analysis and interpretation.
Summary of Findings
The evidence was derived from populations with moderate to severe ischemic LV dysfunction with an overall quality that ranges from moderate to low.
PET appears to be a safe technique for assessing myocardial viability.
CAD patients with moderate to severe ischemic LV dysfunction and residual viable myocardium had significantly lower 2-year mortality rate (3.2%) and higher event-free survival rates (92% at 3 years) when treated with revascularization than those who were not revascularized but were treated medically (16% mortality at 2-years and 48% 3-year event-free survival).
A large meta-analysis and moderate quality studies of diagnostic accuracy consistently showed that compared to other noninvasive diagnostic tests such as thallium SPECT and echocardiography, FDG PET has:
Higher sensitivity (median 90%, range 71%–100%) and better negative likelihood ratio (median 0.16, range 0–0.38; ideal <0.1) for predicting regional myocardial function recovery after revascularization.
Specificity (median 73%, range 33%–91%) that is similar to other radionuclide imaging but lower than that of dobutamine echocardiography
Less useful positive likelihood ratio (median 3.1, range 1.4 –9.2; ideal>10) for predicting segmental function recovery.
Taking positive and negative likelihood ratios together suggests that FDG PET and dobutamine echocardiography may produce small but sometimes important changes in the probability of recovering regional wall motion after revascularization.
Given its higher sensitivity, PET is less likely to produce false positive results in myocardial viability. PET, therefore, has the potential to identify some patients who might benefit from revascularization, but who would not have been identified as suitable candidates for revascularization using thallium SPECT or dobutamine echocardiography.
PET appears to be superior to other nuclear imaging techniques including SPECT with 201thallium or technetium labelled tracers, although recent studies suggest that FDG SPECT may have comparable diagnostic accuracy as FDG PET for predicting regional and global LV function recovery.
No firm conclusion can be reached about the incremental value of PET over other noninvasive techniques for predicting global function improvement or long-term outcomes in the most important target population (patients with severe ischemic LV dysfunction) due to lack of direct comparison.
An Ontario-based economic analysis showed that in people with CAD and severe LV dysfunction and who were found to have no viable myocardium or indeterminate results by thallium SPECT, the use of PET as a follow-up assessment would likely result in lower cost and better 5-year survival compared to the use of thallium SPECT alone. The projected annual budget impact of adding PET under the above scenario was estimated to range from $1.5 million to $2.3 million.
In patients with severe LV dysfunction, that are deemed to have no viable myocardium or indeterminate results in assessments using other noninvasive tests, PET may have a role in further identifying patients who may benefit from revascularization. No firm conclusion can be drawn on the impact of PET viability assessment on long-term clinical outcomes in the most important target population (i.e. patients with severe LV dysfunction).
PMCID: PMC3385418  PMID: 23074467
8.  Optimization of Ordered Subset Expectation Maximization Reconstruction for Reducing Urinary Bladder Artifacts in Single-photon Emission Computed Tomography Imaging 
Bladder artifact during bone single-photon emission computed tomography (SPECT) is a common source of error. The extent and severity of bladder artifacts have been described for filtered back projection (FBP) reconstruction. Ordered subset expectation maximization (OSEM) may help to address this problem of bladder artifacts, which render up to 20% of the SPECT images unreadable. The objective of this study was to evaluate the relationship of the bladder to acetabulum ratio in guiding the choice of the number of iterations and subsets used for OSEM reconstruction, for reducing bladder artifacts found on FBP reconstruction. One hundred five patients with various indications for bone scans were selected and planar and SPECT images were acquired. The SPECT images were reconstructed with both FBP and OSEM using four different combinations of iterations and subsets. The images were given to three experienced nuclear physicians who were blinded to the diagnosis and type of reconstruction used. They then labeled images from the best to the worst after which the data were analyzed. The bladder to acetabulum ratio for each image was determined which was then correlated with the different iterations and subsets used. The study demonstrated that reconstruction using OSEM led to better lesion detectability compared to FBP in 87.62% of cases. It further demonstrated that the iterations and subsets used for reconstruction of an image correlate with the bladder to acetabulum ratio. Four iterations and 8 subsets yielded the best results in 48.5% of the images, whilst 2 iterations and 8 subsets yielded the best results in 33.8%. The number of reconstructed images which yielded the best results with 2 iterations and 8 subsets was the same as or more than those with 4 iterations and 8 subsets when the bladder/acetabulum ratio (A/B) was between 0.2 and 0.39. A ratio below 0.2 or above 0.39 supports the usage of 4 iterations and 8 subsets over 2 iterations and 8 subsets. We conclude that bladder to acetabulum ratio can be used to select the optimum number of iterations and subsets for reconstruction of bone SPECT for accurate characterization of lesions. This study also confirms that reconstruction with OSEM (vs. FBP) leads to better lesion detectability and characterization.
PMCID: PMC3198040  PMID: 22034576
Bladder artifact; bone single-photon emission computed tomography; ordered subset expectation maximization
9.  Non-isotropic noise correlation in PET data reconstructed by FBP but not by OSEM demonstrated using auto-correlation function 
Positron emission tomography (PET) is a powerful imaging technique with the potential of obtaining functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules in a biological system, both in vitro and in vivo. PET images can be used directly or after kinetic modelling to extract quantitative values of a desired physiological, biochemical or pharmacological entity. Because such images are generally noisy, it is essential to understand how noise affects the derived quantitative values. A pre-requisite for this understanding is that the properties of noise such as variance (magnitude) and texture (correlation) are known.
In this paper we explored the pattern of noise correlation in experimentally generated PET images, with emphasis on the angular dependence of correlation, using the autocorrelation function (ACF). Experimental PET data were acquired in 2D and 3D acquisition mode and reconstructed by analytical filtered back projection (FBP) and iterative ordered subsets expectation maximisation (OSEM) methods. The 3D data was rebinned to a 2D dataset using FOurier REbinning (FORE) followed by 2D reconstruction using either FBP or OSEM. In synthetic images we compared the ACF results with those from covariance matrix. The results were illustrated as 1D profiles and also visualized as 2D ACF images.
We found that the autocorrelation images from PET data obtained after FBP were not fully rotationally symmetric or isotropic if the object deviated from a uniform cylindrical radioactivity distribution. In contrast, similar autocorrelation images obtained after OSEM reconstruction were isotropic even when the phantom was not circular. Simulations indicated that the noise autocorrelation is non-isotropic in images created by FBP when the level of noise in projections is angularly variable. Comparison between 1D cross profiles on autocorrelation images obtained by FBP reconstruction and covariance matrices produced almost identical results in a simulation study.
With asymmetric radioactivity distribution in PET, reconstruction using FBP, in contrast to OSEM, generates images in which the noise correlation is non-isotropic when the noise magnitude is angular dependent, such as in objects with asymmetric radioactivity distribution. In this respect, iterative reconstruction is superior since it creates isotropic noise correlations in the images.
PMCID: PMC1142517  PMID: 15892891
10.  Optimization, evaluation, and comparison of standard algorithms for image reconstruction with the VIP-PET 
A novel positron emission tomography (PET) scanner design based on a room-temperature pixelated CdTe solid-state detector is being developed within the framework of the Voxel Imaging PET (VIP) Pathfinder project [1]. The simulation results show a great potential of the VIP to produce high-resolution images even in extremely challenging conditions such as the screening of a human head [2]. With unprecedented high channel density (450 channels/cm3) image reconstruction is a challenge. Therefore optimization is needed to find the best algorithm in order to exploit correctly the promising detector potential. The following reconstruction algorithms are evaluated: 2-D Filtered Backprojection (FBP), Ordered Subset Expectation Maximization (OSEM), List-Mode OSEM (LM-OSEM), and the Origin Ensemble (OE) algorithm. The evaluation is based on the comparison of a true image phantom with a set of reconstructed images obtained by each algorithm. This is achieved by calculation of image quality merit parameters such as the bias, the variance and the mean square error (MSE). A systematic optimization of each algorithm is performed by varying the reconstruction parameters, such as the cutoff frequency of the noise filters and the number of iterations. The region of interest (ROI) analysis of the reconstructed phantom is also performed for each algorithm and the results are compared. Additionally, the performance of the image reconstruction methods is compared by calculating the modulation transfer function (MTF). The reconstruction time is also taken into account to choose the optimal algorithm. The analysis is based on GAMOS [3] simulation including the expected CdTe and electronic specifics.
PMCID: PMC4087273  PMID: 25018777
Medical-image reconstruction methods and algorithms; computer-aided software; Gamma camera; SPECT; PET PET/CT; coronary CT angiography (CTA)
11.  Comparison of List-Mode and DIRECT Approaches for Time-of-Flight PET Reconstruction 
Ieee Transactions on Medical Imaging  2012;31(7):1461-1471.
Early clinical results with time-of-flight (TOF) PET systems have demonstrated the advantages of TOF information in PET reconstruction. Reconstruction approaches in TOF-PET systems include list-mode and binned iterative algorithms as well as confidence-weighted analytic methods. List-mode iterative TOF reconstruction retains the resolutions of the data in the spatial and temporal domains without any binning approximations but is computationally intensive. We have developed an approach [DIRECT (direct image reconstruction for TOF)] to speed up TOF-PET reconstruction that takes advantage of the reduced angular sampling requirement of TOF data by grouping list-mode data into a small number of azimuthal views and co-polar tilts and depositing the grouped events into histo-images, arrays with the sampling and geometry of the final image. All physical effects are included in the system model and deposited in the same histo-image structure. Using histo-images allows efficient computation during reconstruction without ray-tracing or interpolation operations. The DIRECT approach was compared with 3D list-mode TOF ordered subsets expectation maximization (OSEM) reconstruction for phantom and patient data taken on the University of Pennsylvania research LaBr3 TOF-PET scanner. The total processing and reconstruction time for these studies with DIRECT without attention to code optimization is approximately 25–30% that of list-mode TOF-OSEM to achieve comparable image quality. Furthermore, the reconstruction time for DIRECT is independent of the number of events and/or sizes of the spatial and TOF kernels, while the time for list-mode TOFOSEM increases with more events or larger kernels. The DIRECT approach is able to reproduce the image quality of list-mode iterative TOF reconstruction both qualitatively and quantitatively in measured data with a reduced time.
PMCID: PMC3389166  PMID: 22410326
Time-of-flight PET; PET reconstruction
12.  18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for assessment of enteropathy-type T cell lymphoma 
Gut  2003;52(3):347-351.
Background and aims: Enteropathy-type T cell lymphoma (ETCL) represents a relatively rare disease, accounting for less than 1% of non-Hodgkin‘s lymphomas. ETCL is an aggressive lymphoma which may either present de novo or arise in the context of longstanding or untreated coeliac disease (CD). The aim of this study was to evaluate the potential of 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for imaging of ETCL. Furthermore, we wished to evaluate whether the presence of CD might provide a potential diagnostic obstacle to imaging of lymphoma due to unspecific 18F-FDG uptake and whether accumulation of 18F-FDG within the gut correlates with activity of CD.
Patients and methods: We retrospectively analysed patients with ETCL and individuals suffering from CD undergoing 18F-FDG-imaging at our PET unit. Material for histological reassessment by a reference pathologist had to be available for inclusion of patients in the analysis. Whole body 18F-FDG-PET scans were performed 40 minutes following injection of 300–380 MBq of 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake and in case of diffusely elevated intestinal 18F-FDG accumulation, standard uptake values (SUVs) were calculated.
Results: During a period of two years, five patients (one male, four female) with a mean age of 56.4 years (range 44–62) with a diagnosis of ETCL underwent 18F-FDG-PET. Four of these patients were imaged before application of cytotoxic treatment while one patient had regular PET scans for follow up. All four patients undergoing pre-therapeutic imaging showed markedly elevated intestinal 18F-FDG uptake, with a maximal SUV of 6.4–8.0 (mean 7.15 (SD 0.82)). The patient imaged following surgery and cytotoxic therapy had no pathologic 18F-FDG uptake which was found to correlate with normal duodenal mucosa, as evidenced by repeated biopsies and conventional imaging methods. During the same time span, 12 patients (five male, seven female) with a mean age of 63.8 years (range 42–82) suffering from CD were imaged. Four of these patients showed no elevated intestinal 18F-FDG uptake while five had minor diffuse intestinal 18F-FDG accumulation with SUVs ranging between 2.2 and 4.6 (mean 3.4 (SD 0.89)). In the remaining three patients with diffuse intestinal 18F-FDG uptake, no SUV could be calculated. SUVs in patients with ETCL were remarkably higher than in patients suffering from CD (p=0.011), irrespective of the activity of CD at the time of imaging.
Conclusion: In spite of the relatively small number of patients, our results clearly indicate the potential value of 18F-FDG-PET for diagnosing and imaging ETCL. In addition, the data also suggest that 18F-FDG-PET may lead to early diagnosis in individuals developing ETCL in the context of longstanding CD. This is due to the fact that 18F-FDG does not appear to significantly accumulate in the gut of patients with CD, irrespective of disease activity.
PMCID: PMC1773540  PMID: 12584214
18F-FDG-PET; enteropathy-type T cell lymphoma; coeliac disease; refractory sprue
13.  FDG PET/CT Response Evaluation in Malignant Pleural Mesothelioma Patients Treated with Talc Pleurodesis and Chemotherapy 
Journal of Cancer  2012;3:241-245.
Purpose: Talc pleurodesis (TP) is employed worldwide for the management of persistent pneumothorax or pleural effusion, particularly of malignant origin. However, there are very little available data on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (18F FDG PET/CT) response evaluation in malignant pleural mesothelioma (MPM) patients treated with TP and chemotherapy.
Methods: Patients with histologically confirmed MPM underwent TP and FDG PET/CT staging and restaging after 3-4 courses of chemotherapy. All patients fasted and received a dose of 5.18 MBq 18F-FDG per kilogram of body weight. Whole-body emission scans were acquired with and without Ordered Subset Expectation Maximization (OSEM) iterative reconstruction algorithm.
Results: From January 2004 to March 2010, 8 patients with biopsy confirmed MPM (7 epithelial, 1 biphasic), with a median age of 65 years (range: 54-77), were evaluated. Median follow-up was 31 months (range: 4-44). After TP treatment, there was a mean interval of 14 days (range: 9-22) and 125 days (range: 76-162) between FDG PET/CT staging and restaging. According to modified RECIST and EORTC criteria, there was a concordance between the radiologic and metabolic SUVmean and SUVmax responses in 6 (75%) and 3 (37.5%) patients, respectively.
Conclusion: TP produces an increased FDG PET uptake which may interfere with the post-chemotherapy disease evaluation. In our case series, the metabolic response measured by SUVmean seems to be in better agreement with the radiologic response compared to the SUVmax.
PMCID: PMC3366479  PMID: 22670158
18F-FDG PET-CT scan; fluorodeoxyglucose; SUV; talc pleurodesis; malignant pleural mesothelioma.
14.  Role and interpretation of FDG-PET/CT in HIV patients with fever of unknown origin: a prospective study 
Purpose of the study
Fever of unknown origin (FUO) is a challenging clinical entity in HIV patients. FDG-PET/CT is well validated in the work-up of FUO in HIV-negative patients but in HIV viremic patients, metabolism of HIV reactive lymph nodes could decrease its specificity. We prospectively evaluated the usefulness of FDG-PET/CT in FUO in HIV-positive patients and in particular whether HIV viremia impacts on FDG-PET/CT performance.
FDG-PET/CT was performed in 20 HIV patients with FUO and compared with FDG-PET/CT in 10 HIV viremic patients without FUO. Final diagnosis for FUO was based on histopathology, microbiology, or clinical and imaging follow-up. Mode of diagnosis, accordance of FDG-PET/CT with final diagnosis, localization of invasive diagnosis procedures was recorded in order to assess usefulness of FDG-PET/CT.
FDG-PET/CT showed a different pattern in FUO and asymptomatic viremic patients. Reactive HIV lymph nodes in asymptomatic viremic patients were mostly peripheral with mean SUVmax of 6.5. In patients with FUO and underlying focal pathologies, hypermetabolic lymph nodes were central with mean SUVmax of 11.6. Presence of central lymph nodes with high FDG uptake in had a 100% specificity for focal pathology, even in viremic patients and absence of these had 100% negative predictive value. Lymph node biopsy in central hypermetabolic areas allowed identifying underlying disease in all FUO patients. For peripheral lymph nodes, a ROC curve was built in order to define the best cut-off of SUVmax for biopsy: SUVmax of 6–8 showed a sensitivity of 62.5% and specificity of 75%. Lymph nodes with SUVmax<4 had sensitivity of 0%.
FDG-PET/CT contributed to the diagnosis or exclusion of a focal etiology of the febrile state in 80% of HIV patients with FUO. Although number of patients was small, we could highlight several clear-cut features to help interpreting FDG-PET/CT in HIV patients with FUO. As in HIV-negative patients, we showed the usefulness of FDG-PET/CT in FUO in HIV patients even if they are viremic.
PMCID: PMC3512434
15.  18F-FCWAY and 18F-FDG PET in MRI Negative Temporal Lobe Epilepsy 
Epilepsia  2008;50(2):234-239.
Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) shows widespread hypometabolism even in temporal lobe epilepsy (TLE) patients with mesial temporal foci. 18F-trans-4-fluoro-N-2-[4-(2-methoxyphenyl) piperazin-1-yl]ethyl-N-(2-pyridyl)cyclohexanecarboxamide (18F-FCWAY) PET may show more specific 5-HT1A receptor binding reduction in seizure initiation than propagation regions. 18FCWAY PET might be valuable for detecting epileptic foci, and distinguishing mesial from lateral temporal foci in MRI negative TLE patients.
We performed 18F-FCWAY-PET and 18F-FDG-PET in 12 MRI negative TLE patients who had had either surgery or subdural electrode recording, and 15 healthy volunteers. After partial volume correction for brain atrophy, free fraction-corrected volume of distribution (V/f1) measurement and asymmetry indices (AIs) were computed. We compared 18F-FCWAY-PET and 18F-FDG-PET results with scalp video electroencephalography (EEG), invasive EEG and surgical outcome.
Mean 18F-FCWAY V/f1, compared with normal controls, was decreased significantly in fusiform gyrus, hippocampus and parahippocampus ipsilateral to epileptic foci, and AIs significantly greater in hippocampus, parahippocampus, fusiform gyrus, amygdala and inferior temporal regions. Eleven patients had clearly lateralized epileptogenic zones. Nine had congruent, and two non-lateralized, 18F-FCWAY PET. One patient with bitemporal seizure onset had non-lateralized 18F-FCWAY-PET. 18FFDG-PET showed congruent hypometabolism in 7/11 EEG-lateralized patients, bilateral hypometabolic regions in one, contralateral hypometabolism in one, as well as lateralized hypometabolism in the patient with bitemporal subdural seizure onset. Patients with mesial temporal foci tended to have lower superior and mid temporal 18F-FCWAY V/f1 binding AI than those with lateral or diffuse foci.
18F-FCWAY-PET can detect reduced binding in patients with normal MRI, and may be more accurate than 18F-FDG-PET.
PMCID: PMC2642908  PMID: 18801033
Epilepsy; Positron Emission Tomography; Serotonin Receptors; Temporal Lobe; Glucose Metabolism
16.  Influence of the partial volume correction method on 18F-fluorodeoxyglucose brain kinetic modelling from dynamic PET images reconstructed with resolution model based OSEM 
Physics in medicine and biology  2013;58(20):7081-7106.
Kinetic parameters estimated from dynamic 18F-fluorodeoxyglucose PET acquisitions have been used frequently to assess brain function in humans. Neglecting partial volume correction (PVC) for a dynamic series has been shown to produce significant bias in model estimates. Accurate PVC requires a space-variant model describing the reconstructed image spatial point spread function (PSF) that accounts for resolution limitations, including non-uniformities across the field of view due to the parallax effect. For OSEM, image resolution convergence is local and influenced significantly by the number of iterations, the count density, and background-to-target ratio. As both count density and background-to-target values for a brain structure can change during a dynamic scan, the local image resolution may also concurrently vary. When PVC is applied post-reconstruction the kinetic parameter estimates may be biased when neglecting the frame-dependent resolution. We explored the influence of the PVC method and implementation on kinetic parameters estimated by fitting 18F-fluorodeoxyglucose dynamic data acquired on a dedicated brain PET scanner and reconstructed with and without PSF modelling in the OSEM algorithm. The performance of several PVC algorithms was quantified with a phantom experiment, an anthropomorphic Monte Carlo simulation, and a patient scan. Using the last frame reconstructed image only for regional spread function (RSF) generation, as opposed to computing RSFs for each frame independently, and applying perturbation GTM PVC with PSF based OSEM produced the lowest magnitude bias kinetic parameter estimates in most instances, although at the cost of increased noise compared to the PVC methods utilizing conventional OSEM. Use of the last frame RSFs for PVC with no PSF modelling in the OSEM algorithm produced the lowest bias in CMRGlc estimates, although by less than 5% in most cases compared to the other PVC methods. The results indicate that the PVC implementation and choice of PSF modelling in the reconstruction can significantly impact model parameters.
PMCID: PMC4234075  PMID: 24052021
partial volume effect correction; PET; cerebral-metabolism; quantitation; OSEM
17.  Advanced [18F]FDG and [11C]flumazenil PET analysis for individual outcome prediction after temporal lobe epilepsy surgery for hippocampal sclerosis 
NeuroImage : Clinical  2014;7:122-131.
We have previously shown that an imaging marker, increased periventricular [11C]flumazenil ([11C]FMZ) binding, is associated with failure to become seizure free (SF) after surgery for temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS). Here, we investigated whether increased preoperative periventricular white matter (WM) signal can be detected on clinical [18F]FDG-PET images. We then explored the potential of periventricular FDG WM increases, as well as whole-brain [11C]FMZ and [18F]FDG images analysed with random forest classifiers, for predicting surgery outcome.
Sixteen patients with MRI-defined HS had preoperative [18F]FDG and [11C]FMZ-PET. Fifty controls had [18F]FDG-PET (30), [11C]FMZ-PET (41), or both (21). Periventricular WM signal was analysed using Statistical Parametric Mapping (SPM8), and whole-brain image classification was performed using random forests implemented in R ( Surgery outcome was predicted at the group and individual levels.
At the group level, non-seizure free (NSF) versus SF patients had periventricular increases with both tracers. Against controls, NSF patients showed more prominent periventricular [11C]FMZ and [18F]FDG signal increases than SF patients. All differences were more marked for [11C]FMZ. For individuals, periventricular WM signal increases were seen at optimized thresholds in 5/8 NSF patients for both tracers. For SF patients, 1/8 showed periventricular signal increases for [11C]FMZ, and 4/8 for [18F]FDG. Hence, [18F]FDG had relatively poor sensitivity and specificity. Random forest classification accurately identified 7/8 SF and 7/8 NSF patients using [11C]FMZ images, but only 4/8 SF and 6/8 NSF patients with [18F]FDG.
This study extends the association between periventricular WM increases and NSF outcome to clinical [18F]FDG-PET, but only at the group level. Whole-brain random forest classification increases [11C]FMZ-PET's performance for predicting surgery outcome.
Graphical abstract
PMCID: PMC4299974  PMID: 25610774
Hippocampal sclerosis; Surgery outcome; FDG-PET; FMZ-PET; Periventricular white matter signal increases; Random forests
18.  Is 11C-flumazenil PET superior to 18FDG PET and 123I-iomazenil SPECT in presurgical evaluation of temporal lobe epilepsy? 
OBJECTIVE: To determine the contribution of 18FDG PET, 11C-flumazenil PET, and 123I-iomazenil SPECT to the presurgical evaluation of patients with medically intractable complex partial seizures. METHODS: Presurgical evaluation was performed in 23 patients, who were considered candidates for temporal lobe resective surgery (14 females and nine males with a median age of 34 (range 13 to 50) years). The presurgical diagnosis was based on seizure semiology as demonstrated with ictal video recording, ictal and interictal scalp EEG recordings, and MRI. RESULTS: Eighteen patients had convergent findings in clinical semiology, interictal and ictal EEG with scalp and sphenoidal electrodes, and MRI that warranted surgery without depth EEG (DEEG). In five patients with insufficient precision of localisation, DEEG with intracerebral and subdural electrodes was performed. MRI showed abnormalities in 22 out of 23 patients. Of these 22, 18 had mesial temporal sclerosis. This was limited to the mesial temporal lobe in four and more widespread in the temporal lobe in 14 patients. In one patient only enlargement of the temporal horn was found and in three others only white matter lesions were detected. 18FDG PET showed a large area of glucose hypometabolism in the epileptogenic temporal lobe, with an extension outside the temporal lobe in 10 of 23 patients. Only in one of these patients DEEG showed extratemporal abnormalities that were concordant with a significant extratemporal extension of hypometabolism in 18FDG PET. 18FDG PET was compared with the results of scalp EEG: in none of the patients was an anterior temporal ictal onset in scalp EEG related to a maximum hypometabolism in the mesial temporal area. By contrast, the region of abnormality indicated by 11C-flumazenil PET was much more restricted, also when compared with DEEG findings. Extension of abnormality outside the lobe of surgery was seen in only two patients with 11C-flumazenil and was less pronounced compared with the intratemporal abnormality. Both 18FDG PET and 11C-flumazenil PET reliably indicated the epileptogenic temporal lobe. Thus these techniques provide valuable support for the presurgical diagnosis, especially in patients with non-lesional MRI or non-lateralising or localising scalp EEG recordings. In those patients in whom phase 1 presurgical evaluation on the basis of classic methods does not allow a localisation of the epileptogenic area, PET studies may provide valuable information for the strategy of the implantation of intracranial electrodes for DEEG. Previous studies have suggested that 11C-flumazenil binding has a closer spatial relationship with the zone of ictal onset than the area of glucose hypometabolism, but this study suggests rather that the decrease in the 11C-flumazenil binding simply reflects a loss of neurons expressing the benzodiazepine-GABA receptor. 11C-flumazenil PET did not prove to be superior to 18FDG PET. CONCLUSION: In 21 patients sufficient material was obtained at surgery for a pathological examination. In 17 mesial temporal sclerosis, in one an oligodendroglioma grade B, in another a vascular malformation and in two patients no abnormalities were found. Although all 21 patients with pathological abnormality showed hypometabolic zones with 18FDG PET and a decreased uptake in 11C-flumazenil binding, there was no strong correlation between pathological diagnosis and functional abnormal areas in PET. Grading of medial temporal sclerosis according to the Wyler criteria showed no correlation with the degree of hypometabolism in either 18FDG or 11C-flumazenil PET. The interictal 123I-iomazenil SPECT technique was highly inaccurate in localising the lobe of surgery.
PMCID: PMC486725  PMID: 9048714
19.  Impact on Image Noise of Incorporating Detector Blurring into Image Reconstruction for a Small Animal PET Scanner 
IEEE transactions on nuclear science  2009;56(5):2769-2776.
We study the noise characteristics of an image reconstruction algorithm that incorporates a model of the non-stationary detector blurring (DB) for a mouse-imaging positron emission tomography (PET) scanner. The algorithm uses ordered subsets expectation maximization (OSEM) image reconstruction, which is used to suppress statistical noise. Including the non-stationary detector blurring in the reconstruction process (OSEM(DB)) has been shown to increase contrast in images reconstructed from measured data acquired on the fully-3D MiCES PET scanner developed at the University of Washington. As an extension, this study uses simulation studies with a fully-3D acquisition mode and our proposed FORE+OSEM(DB) reconstruction process to evaluate the volumetric contrast versus noise trade-offs of this approach. Multiple realizations were simulated to estimate the true noise properties of the algorithm. The results show that incorporation of detector blurring (FORE+OSEM(DB)) into the reconstruction process improves the contrast/noise trade-offs compared to FORE+OSEM in a radially dependent manner. Adding post reconstruction 3D Gaussian smoothing to FORE+OSEM and FORE+OSEM(DB) reduces the contrast versus noise advantages of FORE+OSEM(DB).
PMCID: PMC2805005  PMID: 20161545
20.  Surgical decision making in Temporal Lobe Epilepsy (TLE): a comparison of 18Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET), MRI, and EEG 
Epilepsy & behavior : E&B  2011;22(2):293-297.
(1) Determine the effect of 18Fluorodeoxyglucose Positron Emission Tomography (FDG-PET), magnetic resonance imaging (MRI), and electroencephalogram (EEG) on the decision for temporal lobe epilepsy (TLE) surgery. (2) Determine if FDG-PET, MRI, or EEG predict surgical outcome.
All PET scans ordered (2000–2010) for epilepsy or seizure were tabulated. Medical records were investigated to determine eligibility and collect data. Statistical analysis included odds ratios, kappa statistics, univariate analysis, and logistic regression.
186 patients had an FDG-PET, 124 patients had TLE, 50 were surgical candidates, and 27 had operations with > 6 months follow-up. Median length of follow-up was 24 months. MRI, FDG-PET, and EEG were significant predictors of surgical candidacy (p<0.001) with odds ratio of 42.8, 20.4, and 6.3 respectively. PET was the only significant predictor of post-operative outcome. (p<0.01)
MRI had a trend toward most influence on surgical candidacy, but only FDG-PET predicted the surgical outcome.
PMCID: PMC3260654  PMID: 21798813
temporal lobe epilepsy; medication refractory epilepsy; epilepsy surgery; fluorodeoxyglucose (FDG); positron emission tomography (PET); magnetic resonance imaging (MRI); Electroencephalogram (EEG)
21.  Presurgical Multimodality Neuroimaging in Electroencephalographic Lateralized Temporal Lobe Epilepsy 
Annals of neurology  1997;42(6):829-837.
The purpose of this study was to compare 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), hippocampal volumetry (HV), T2 relaxometry, and proton magnetic resonance spectroscopic imaging (1H-MRSI) in the presurgical neuroimaging lateralization of patients with nonlesional, electroencephalogram (EEG)-defined unilateral temporal lobe epilepsy (TLE). Twenty-five patients were prospectively studied, along with age-matched controls. T2 relaxometry examinations were performed in 13 patients. Comparison of FDG-PET, HV, and 1H-MRSI was possible in 23 patients. FDG-PET lateralized 87% of patients, HV 65%, N-acetyl aspartate (NAA)/(choline [Cho] + creatine [Cr]) 61%, and [NAA] 57%. Combined HV and NAA/(Cho + Cr) results lateralized 83% of the patients, a value similar to PET. Of 10 patients with normal magnetic resonance imaging (MRI) scans, 2 were lateralized with HV, 6 with FDG-PET, 4 with NAA/(Cho + Cr), and 3 with [NAA]. T2 relaxometry lateralized no patients without hippocampal atrophy. Bilateral abnormality was present in 29 to 33% of patients with 1H-MRSI measures and 17% with HV. Only hippocampal atrophy correlated with postoperative seizure-free outcome. FDG-PET remains the most sensitive imaging method to correlate with EEG-lateralized TLE. Both FDG-PET and 1H-MRSI can lateralize patients with normal MRI, but only the presence of relative unilateral hippocampal atrophy is predictive of seizure-free outcome. Bilaterally abnormal MRI and 1H-MRSI measures do not preclude good surgical outcome.
PMCID: PMC2709486  PMID: 9403474
22.  Objective Detection of Epileptic Foci by 18F-FDG PET in Children Undergoing Epilepsy Surgery 
PET has been used for the presurgical localization of epileptic foci for more than 20 y; still, its clinical role in children with intractable epilepsy remains unclear, largely because of variable analytic approaches and different outcome measures. The purpose of the present study was to evaluate and optimize the performance (lateralization and lobar localization value of epileptic foci) of objective voxel-based analysis of 18F-FDG PET scans in a pediatric epilepsy population.
Twenty children with intractable focal epilepsy (mean age ± SD, 11 ± 4 y; age range, 6–18 y) who underwent interictal 18F-FDG PET, followed by 2-stage epilepsy surgery with chronic subdural electrocorticographic monitoring, and were seizure-free after surgery were included in this study. PET images were analyzed using both a visual-analysis and a statistical parametric mapping (SPM) method. Lateralization value and performance of lobar localization (in lateral and medial surfaces of all lobes, total of 8 regions in each epileptic hemisphere), calculated for 3 different statistical thresholds, were determined against intracranial electrocorticography-determined seizure-onset region and surgical resection site.
SPM using a statistical threshold of P less than 0.001 provided 100% correct lateralization, which was better than visual assessment (90%). Although visual and SPM analyses (with both P < 0.001 and P < 0.0001 thresholds) performed similarly well (with a sensitivity and specificity of 74%or above) in the localization of seizure-onset regions, SPM detected 7 of 9 seizure-onset regions, mostly in medial cortices, that were missed by visual assessment. Also, SPM performed equally well in both hemispheres, compared with visual analysis, which performed better in the left hemisphere. No statistical difference in performance was observed between visual and SPM analyses of children with abnormal versus normal MRI findings or of children with gliosis versus developmental pathology. Clinical variables, such as age, duration of epilepsy, age of seizure onset, and time between PET and last seizure, showed no correlation with sensitivity or specificity of either visual analysis or SPM analysis.
SPM analysis, using a young adult control group, can be used as a complementary objective analytic method in identifying epileptogenic lobar regions by 18F-FDG PET in children older than 6 y.
PMCID: PMC3157889  PMID: 21078805
children; 18F-FDG PET; epilepsy; epilepsy surgery; statistical parametric mapping
23.  Theoretical and Numerical Study of MLEM and OSEM Reconstruction Algorithms for Motion Correction in Emission Tomography 
IEEE transactions on nuclear science  2009;56(5):2739-2749.
Patient body-motion and respiratory-motion impacts the image quality of cardiac SPECT and PET perfusion images. Several algorithms exist in the literature to correct for motion within the iterative maximum-likelihood reconstruction framework. In this work, three algorithms are derived starting with Poisson statistics to correct for patient motion. The first one is a motion compensated MLEM algorithm (MC-MLEM). The next two algorithms called MGEM-1 and MGEM-2 (short for Motion Gated OSEM, 1 and 2) use the motion states as subsets, in two different ways. Experiments were performed with NCAT phantoms (with exactly known motion) as the source and attenuation distributions. Experiments were also performed on an anthropomorphic phantom and a patient study. The SIMIND Monte Carlo simulation software was used to create SPECT projection images of the NCAT phantoms. The projection images were then modified to have Poisson noise levels equivalent to that of clinical acquisition. We investigated application of these algorithms to correction of (1) a large body-motion of 2 cm in Superior-Inferior (SI) and Anterior-Posterior (AP) directions each and (2) respiratory motion of 2 cm in SI and 0.6 cm in AP. We determined the bias with respect to the NCAT phantom activity for noiseless reconstructions as well as the bias-variance for noisy reconstructions. The MGEM-1 advanced along the bias-variance curve faster than the MC-MLEM with iterations. The MGEM-1 also lowered the noiseless bias (with respect to NCAT truth) faster with iterations, compared to the MC-MLEM algorithms, as expected with subset algorithms. For the body motion correction with two motion states, after the 9th iteration the bias was close to that of MC-MLEM at iteration 17, reducing the number of iterations by a factor of 1.89. For the respiratory motion correction with 9 motion states, based on the noiseless bias, the iteration reduction factor was approximately 7. For the MGEM-2, however, bias-plot or the bias-variance-plot saturated with iteration because of successive interpolation error. SPECT data was acquired simulating respiratory motion of 2 cm amplitude with an anthropomorphic phantom. A patient study acquired with body motion in a second rest was also acquired. The motion correction was applied to these acquisitions with the anthropomorphic phantom and the patient study, showing marked improvements of image quality with the estimated motion correction.
PMCID: PMC2858434  PMID: 20419053
Expectation maximization algorithm; image reconstruction
24.  Harmonizing SUVs in multicentre trials when using different generation PET systems: prospective validation in non-small cell lung cancer patients 
We prospectively evaluated whether a strategy using point spread function (PSF) reconstruction for both diagnostic and quantitative analysis in non-small cell lung cancer (NSCLC) patients meets the European Association of Nuclear Medicine (EANM) guidelines for harmonization of quantitative values.
The NEMA NU-2 phantom was used to determine the optimal filter to apply to PSF-reconstructed images in order to obtain recovery coefficients (RCs) fulfilling the EANM guidelines for tumour positron emission tomography (PET) imaging (PSFEANM). PET data of 52 consecutive NSCLC patients were reconstructed with unfiltered PSF reconstruction (PSFallpass), PSFEANM and with a conventional ordered subset expectation maximization (OSEM) algorithm known to meet EANM guidelines. To mimic a situation in which a patient would undergo pre- and post-therapy PET scans on different generation PET systems, standardized uptake values (SUVs) for OSEM reconstruction were compared to SUVs for PSFEANM and PSFallpass reconstruction.
Overall, in 195 lesions, Bland-Altman analysis demonstrated that the mean ratio between PSFEANM and OSEM data was 1.03 [95 % confidence interval (CI) 0.94–1.12] and 1.02 (95 % CI 0.90–1.14) for SUVmax and SUVmean, respectively. No difference was noticed when analysing lesions based on their size and location or on patient body habitus and image noise. Ten patients (84 lesions) underwent two PET scans for response monitoring. Using the European Organization for Research and Treatment of Cancer (EORTC) criteria, there was an almost perfect agreement between OSEMPET1/OSEMPET2 (current standard) and OSEMPET1/PSFEANM-PET2 or PSFEANM-PET1/OSEMPET2 with kappa values of 0.95 (95 % CI 0.91–1.00) and 0.99 (95 % CI 0.96–1.00), respectively. The use of PSFallpass either for pre- or post-treatment (i.e. OSEMPET1/PSFallpass-PET2 or PSFallpass-PET1/OSEMPET2) showed considerably less agreement with kappa values of 0.75 (95 % CI 0.67–0.83) and 0.86 (95 % CI 0.78–0.94), respectively.
Protocol-optimized images and compliance with EANM guidelines allowed for a reliable pre- and post-therapy evaluation when using different generation PET systems. These data obtained in NSCLC patients could be extrapolated to other solid tumours.
Electronic supplementary material
The online version of this article (doi:10.1007/s00259-013-2391-1) contains supplementary material, which is available to authorized users.
PMCID: PMC3679414  PMID: 23564036
PET; Multicentre trials; PSF; NSCLC; SUV; Tumour imaging
25.  Design of 20-aperture multipinhole collimator and performance evaluation for myocardial perfusion imaging application 
Physics in medicine and biology  2013;58(20):10.1088/0031-9155/58/20/7209.
Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) remains a critical tool in the diagnosis of coronary artery disease (CAD). However, after more than three decades of use, photon detection efficiency remains poor and unchanged. This is due to the continued reliance on parallel-hole collimators first introduced in 1964. These collimators possess poor geometric efficiency. Here we present the performance evaluation results of a newly designed multipinhole collimator with 20 pinhole apertures (PH20) for commercial SPECT systems. Computer simulations and numerical observer studies were used to assess the noise, bias and diagnostic imaging performance of a PH20 collimator in comparison with those of a low energy high resolution (LEHR) parallel-hole collimator. Ray-driven projector/backprojector pairs were used to model SPECT imaging acquisitions, including simulation of noiseless projection data and performing MLEM/OSEM image reconstructions. Poisson noise was added to noiseless projections for realistic projection data. Noise and bias performance were investigated for five mathematical cardiac and torso (MCAT) phantom anatomies imaged at two gantry orbit positions (19.5 cm and 25.0 cm). PH20 and LEHR images were reconstructed with 300 MLEM iterations and 30 OSEM iterations (10 subsets), respectively. Diagnostic imaging performance was assessed by a receiver operating characteristic (ROC) analysis performed on a single MCAT phantom; however, in this case PH20 images were reconstructed with 75 pixel-based OSEM iterations (4 subsets). Four PH20 projection views from two positions of a dual-head camera acquisition and sixty LEHR projections were simulated for all studies. At uniformly-imposed resolution of 12.5 mm, significant improvements in SNR and diagnostic sensitivity (represented by the area under the ROC curve, or AUC) were realized when PH20 collimators are substituted for LEHR parallel- hole collimators. SNR improves by factors of 1.94-2.34 for the five patient anatomies and two orbital positions studied. For the ROC analysis the PH20 AUC is larger than the LEHR AUC with a p-value of 0.0067. Bias performance, however, decreases with the use of PH20 collimators. Systematic analyses showed PH20 collimators present improved diagnostic imaging performance over LEHR collimators, requiring only collimator exchange on existing SPECT cameras for their use.
PMCID: PMC3855225  PMID: 24061162

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