Validation of the physiological background correction method for the suppression of the spill-in effect near highly radioactive regions in positron emission tomography

BACKGROUND: Positron emission tomography (PET) imaging has a wide applicability in oncology, cardiology and neurology. However, a major drawback when imaging very active regions such as the bladder is the spill-in effect, leading to inaccurate quantification and obscured visualisation of nearby lesions. Therefore, this study aims at investigating and correcting for the spill-in effect from high-activity regions to the surroundings as a function of activity in the hot region, lesion size and location, system resolution and application of post-filtering using a recently proposed background correction technique. This study involves analytical simulations for the digital XCAT2 phantom and validation acquiring NEMA phantom and patient data with the GE Signa PET/MR scanner. Reconstructions were done using the ordered subset expectation maximisation (OSEM) algorithm. Dedicated point-spread function (OSEM+PSF) and a recently proposed background correction (OSEM+PSF+BC) were incorporated into the reconstruction for spill-in correction. The standardised uptake values (SUV) were compared for all reconstruction algorithms. RESULTS: The simulation study revealed that lesions within 15-20 mm from the hot region were predominantly affected by the spill-in effect, leading to an increased bias and impaired lesion visualisation within the region. For OSEM, lesion SUVmax converged to the true value at low bladder activity, but as activity increased, there was an overestimation as much as 19% for proximal lesions (distance around 15-20 mm from the bladder edge) and 2-4% for distant lesions (distance larger than 20 mm from the bladder edge). As bladder SUV increases, the % SUV change for proximal lesions is about 31% and 6% for SUVmax and SUVmean, respectively, showing that the spill-in effect is more evident for the SUVmax than the SUVmean. Also, the application of post-filtering resulted in up to 65% increment in the spill-in effect around the bladder edges. For proximal lesions, PSF has no major improvement over OSEM because of the spill-in effect, coupled with the blurring effect by post-filtering. Within two voxels around the bladder, the spill-in effect in OSEM is 42% (32%), while for OSEM+PSF, it is 31% (19%), with (and without) post-filtering, respectively. But with OSEM+PSF+BC, the spill-in contribution from the bladder was relatively low (below 5%, either with or without post-filtering). These results were further validated using the NEMA phantom and patient data for which OSEM+PSF+BC showed about 70-80% spill-in reduction around the bladder edges and increased contrast-to-noise ratio up to 36% compared to OSEM and OSEM+PSF reconstructions without post-filtering. CONCLUSION: The spill-in effect is dependent on the activity in the hot region, lesion size and location, as well as post-filtering; and this is more evident in SUVmax than SUVmean. However, the recently proposed background correction method facilitates stability in quantification and enhances the contrast in lesions with low uptake

Improved identification of abdominal aortic aneurysm using the Kernelized Expectation Maximization algorithm

Abdominal aortic aneurysm (AAA) monitoring and risk of rupture is currently assumed to be correlated with the aneurysm diameter. Aneurysm growth, however, has been demonstrated to be unpredictable. Using PET to measure uptake of [18F]-NaF in calcified lesions of the abdominal aorta has been shown to be useful for identifying AAA and to predict its growth. The PET low spatial resolution, however, can affect the accuracy of the diagnosis. Advanced edge-preserving reconstruction algorithms can overcome this issue. The kernel method has been demonstrated to provide noise suppression while retaining emission and edge information. Nevertheless, these findings were obtained using simulations, phantoms and a limited amount of patient data. In this study, the authors aim to investigate the usefulness of the anatomically guided kernelized expectation maximization (KEM) and the hybrid KEM (HKEM) methods and to judge the statistical significance of the related improvements. Sixty-one datasets of patients with AAA and 11 from control patients were reconstructed with ordered subsets expectation maximization (OSEM), HKEM and KEM and the analysis was carried out using the target-to-blood-pool ratio, and a series of statistical tests. The results show that all algorithms have similar diagnostic power, but HKEM and KEM can significantly recover uptake of lesions and improve the accuracy of the diagnosis by up to 22% compared to OSEM. The same improvements are likely to be obtained in clinical applications based on the quantification of small lesions, like for example cancer

A potent betulinic acid analogue ascertains an antagonistic mechanism between autophagy and proteasomal degradation pathway in HT-29 cells

Betulinic acid (BA), a member of pentacyclic triterpenes has shown important biological activities like anti-bacterial, anti-malarial, anti-inflammatory and most interestingly anticancer property. To overcome its poor aqueous solubility and low bioavailability, structural modifications of its functional groups are made to generate novel lead(s) having better efficacy and less toxicity than the parent compound. BA analogue, 2c was found most potent inhibitor of colon cancer cell line, HT-29 cells with IC50 value 14.9 μM which is significantly lower than standard drug 5-fluorouracil as well as parent compound, Betulinic acid. We have studied another mode of PCD, autophagy which is one of the important constituent of cellular catabolic system as well as we also studied proteasomal degradation pathway to investigate whole catabolic pathway after exploration of 2c on HT-29 cells. Mechanism of autophagic cell death was studied using fluorescent dye like acridine orange (AO) and monodansylcadaverin (MDC) staining by using fluorescence microscopy. Various autophagic protein expression levels were determined by Western Blotting, qRT-PCR and Immunostaining. Confocal Laser Scanning Microscopy (CLSM) was used to study the colocalization of various autophagic proteins. These were accompanied by formation of autophagic vacuoles as revealed by FACS and transmission electron microscopy (TEM). Proteasomal degradation pathway was studied by proteasome-Glo™ assay systems using luminometer.The formation of autophagic vacuoles in HT-29 cells after 2c treatment was determined by fluorescence staining – confirming the occurrence of autophagy. In addition, 2c was found to alter expression levels of different autophagic proteins like Beclin-1, Atg 5, Atg 7, Atg 5-Atg 12, LC3B and autophagic adapter protein, p62. Furthermore we found the formation of autophagolysosome by colocalization of LAMP-1 with LC3B, LC3B with Lysosome, p62 with lysosome. Finally, as proteasomal degradation pathway downregulated after 2c treatment colocalization of ubiquitin with lysosome and LC3B with p62 was studied to confirm that protein degradation in autophagy induced HT-29 cells follows autolysosomal pathway. In summary, betulinic acid analogue, 2c was able to induce autophagy in HT-29 cells and as proteasomal degradation pathway downregulated after 2c treatment so protein degradation in autophagy induced HT-29 cell

Assessment of different quantification metrics of [¹⁸F]-NaF PET/CT images of patients with abdominal aortic aneurysm

Background: We aim to assess the spill-in effect and the benefit in quantitative accuracy for [18F]-NaF PET/CT imaging of abdominal aortic aneurysms (AAA) using the background correction (BC) technique. Methods: Seventy-two datasets of patients diagnosed with AAA were reconstructed with ordered subset expectation maximization algorithm incorporating point spread function (PSF). Spill-in effect was investigated for the entire aneurysm (AAA), and part of the aneurysm excluding the region close to the bone (AAAexc). Quantifications of PSF and PSF+BC images using different thresholds (% of max. SUV in target regions-of-interest) to derive target-to-background (TBR) values (TBRmax, TBR90, TBR70 and TBR50) were compared at 3 and 10 iterations. Results: TBR differences were observed between AAA and AAAexc due to spill-in effect from the bone into the aneurysm. TBRmax showed the highest sensitivity to the spill-in effect while TBR50 showed the least. The spill-in effect was reduced at 10 iterations compared to 3 iterations, but at the expense of reduced contrast-to-noise ratio (CNR). TBR50 yielded the best trade-off between increased CNR and reduced spill-in effect. PSF+BC method reduced TBR sensitivity to spill-in effect, especially at 3 iterations, compared to PSF (P-value ≤ 0.05). Conclusion: TBR50 is robust metric for reduced spill-in and increased CNR

Iterative reconstruction incorporating background correction improves quantification of [18F]-NaF PET/CT images of patients with abdominal aortic aneurysm

Background A confounding issue in [18F]-NaF PET/CT imaging of abdominal aortic aneurysms (AAA) is the spill in contamination from the bone into the aneurysm. This study investigates and corrects for this spill in contamination using the background correction (BC) technique without the need to manually exclude the part of the AAA region close to the bone. Methods Seventy-two (72) datasets of patients with AAA were reconstructed with the standard ordered subset expectation maximization (OSEM) algorithm incorporating point spread function (PSF) modelling. The spill in effect in the aneurysm was investigated using two target regions of interest (ROIs): one covering the entire aneurysm (AAA), and the other covering the aneurysm but excluding the part close to the bone (AAAexc). ROI analysis was performed by comparing the maximum SUV in the target ROI (SUVmax(T)), the corrected cSUVmax (SUVmax(T) − SUVmean(B)) and the target-to-blood ratio (TBR = SUVmax(T)/SUVmean(B)) with respect to the mean SUV in the right atrium region. Results There is a statistically significant higher [18F]-NaF uptake in the aneurysm than normal aorta and this is not correlated with the aneurysm size. There is also a significant difference in aneurysm uptake for OSEM and OSEM + PSF (but not OSEM + PSF + BC) when quantifying with AAA and AAAexc due to the spill in from the bone. This spill in effect depends on proximity of the aneurysms to the bone as close aneurysms suffer more from spill in than farther ones. Conclusion The background correction (OSEM + PSF + BC) technique provided more robust AAA quantitative assessments regardless of the AAA ROI delineation method, and thus it can be considered as an effective spill in correction method for [18F]-NaF AAA studies

The Impact of Mobile Phone Penetration on African Inequality

The aim of this paper is to complement theoretical and qualitative literature with empirical evidence on the income-redistributive effect of mobile phone penetration in 52 African countries. It deviates from mainstream country-specific and microeconomic survey-based approaches in the literature and provides the first macroeconomic assessment of the ‘mobile phone’-inequality nexus. The findings suggest that mobile penetration is pro-poor, as it has a positive income equality effect. ‘Mobile phone’-oriented poverty reduction channels are discussed

Effects of balanced scorecard on performance of firms in the service sector

This study sought to establish the effects of the Balanced Scorecard (BSC) on performance of firms in the service sector. The study location was in Kakamega Municipality, Kenya and a survey research design involving 200 service providing firms was utilized. Stratified random sampling procedure was adopted with the strata organized based on the nature of services offered. After the stratification,simple random sampling was utilized to select the respondent firms. Semi-structured questionnaires were employed to collect primary data which were analyzed through descriptive statistics. The study revealed that non-financial criteria are as important as financial criteria in measurement systems and when both measures are integrated in the system, they lead to superior results

Molecular diagnosis of Plasmodium ovale by photo-induced electron transfer fluorogenic primers: PET-PCR.

Accurate diagnosis of malaria infections continues to be challenging and elusive, especially in the detection of submicroscopic infections. Developing new malaria diagnostic tools that are sensitive enough to detect low-level infections, user friendly, cost effective and capable of performing large scale diagnosis, remains critical. We have designed novel self-quenching photo-induced electron transfer (PET) fluorogenic primers for the detection of P. ovale by real-time PCR. In our study, a total of 173 clinical samples, consisting of different malaria species, were utilized to test this novel PET-PCR primer. The sensitivity and specificity were calculated using nested-PCR as the reference test. The novel primer set demonstrated a sensitivity of 97.5% and a specificity of 99.2% (95% CI 85.2-99.8% and 95.2-99.9% respectively). Furthermore, the limit of detection for P. ovale was found to be 1 parasite/μl. The PET-PCR assay is a new molecular diagnostic tool with comparable performance to other commonly used PCR methods. It is relatively easy to perform, and amiable to large scale malaria surveillance studies and malaria control and elimination programs. Further field validation of this novel primer will be helpful to ascertain the utility for large scale malaria screening programs