ABSTRACT PURPOSE To develop a complete image analysis and quantification framework that accuratel... more ABSTRACT PURPOSE To develop a complete image analysis and quantification framework that accurately determines disease severity and its progression in pulmonary infections using three small animal models—rabbit, ferret, and mouse. METHOD AND MATERIALS We designed a fast and robust automated image analysis platform with a quantification tool that facilitates accurate quantification of pulmonary lesions, and an image registration pipeline that supports a volumetric comparison of all serial scans using PET and CT images. The proposed method for analysis contained three steps: (i) the lung was segmented via an interactive region growing method (ii) mathematical morphology was then applied to this binary mask to remove all non-lung regions from the images; and (iii) then the affinity propagation based clustering algorithm was used on all PET images to precisely segment the high uptake regions. The proposed framework was tested using sequentially acquired CT and PET images. The rabbits were infected with Mycobacterium tuberculosis (TB) (92 PET-CT scans). The ferrets were injected with the H1N1 influenza virus (44 PET-CT scans), and the mice were infected with an aerosolized respiratory pathogen (24 PET-CT scans). Segmentations were evaluated by expert radiologists and compared with ground truth segmentations. RESULTS Each small animal model was evaluated within the same animal type and the Dice Similarity Coefficient (DSC), and the Haussdorf distance (HD) were used for evaluation of the proposed method. The estimated lesion volume sizes from CT and PET images, estimated from the proposed method and the ground truth (R2=0.8922, p<0.01 and R2=0.8664, p<0.01, respectively), were significant. The DSC(%) was 93.4±4.5% for normal lung CT scans and 86.0±7.1% for pathological lung CT scans. Similarly, a DSC of 89.06±9.83% was obtained for PET images. Experiments showed excellent agreements (all above 85%), with expert evaluations for both structural and functional imaging modalities. CONCLUSION The proposed computational framework can increase the efficiency and quality of pre-clinical findings relative to clinical standards and decrease the inter-observer variation from manual quantification methods that can obscure findings. CLINICAL RELEVANCE/APPLICATION This framework can be applied clinically for accurate, efficicent, and robust quantification of infectious diseases using longitudinal PET-CT images.
ABSTRACT PURPOSE To develop a novel segmentation method that can identify and quantify diffuse an... more ABSTRACT PURPOSE To develop a novel segmentation method that can identify and quantify diffuse and multi-focal uptake regions using small animal model PET images that have a diagnosis of a pulmonary infection. METHOD AND MATERIALS Our segmentation approach is based on affinity propagation (AP) clustering and uses a novel distance metric and a probability density function that is estimated from a smoothed histogram. An overview of the proposed method is as follows: (i) the PET image histogram was estimated and smoothed by using a diffusion based kernel density estimation, (ii) a novel similarity function was constructed to determine how similar the histogram data points are to each other, based on two constraints: probability based and intensity based constraints, with the assumption that points that are more similar are more likely to belong to the same classification, and (iii) the AP clustering was applied to the similarities between the data points in order to find optimal thresholding levels that can separate the significant uptake regions into several tissue labels. Our proposed method was tested using an infectious disease small animal model that consisted of imaging ten rabbits at weeks 0,5,10,15,20,30, and 38 with FDG-PET—and all rabbits were infected with an aerosolized Mycobacterium Tuberculosis. Two experts segmented the images to define the ground truth for comparison. RESULTS The Dice Similarity Coefficient (DSC) and the sensitivity and specificity were calculated between the segmentation regions that were found by the proposed method and then compared to expert delineations. An average DSC of 89.06±9.82% with a sensitivity of 97.87±7.09% and a specificity of 83.70±15.32% were achieved. The Pearson correlation coefficient between the delineation performances of the two expert observers was R2=0.85 (p<0.01), while the correlation coefficient between the proposed method and the average of the observers segmentations was R2=0.91 (p<0.01). CONCLUSION Current PET segmentation techniques focus on focal uptake regions and are not well suited for multi-focal uptake regions, commonly found in infectious lung diseases. Our proposed segmentation method quantified the multi-focal uptake regions with high accuracy and within seconds—and it outperformed the state-of-the-art methods. CLINICAL RELEVANCE/APPLICATION This method can be used to segment diffuse and multi-focal FDG uptake normally seen in PET images from patients with infectious diseases like TB.
International journal of biological macromolecules, Jan 13, 2015
Folic Acid conjugated liposomes encapsulating Oxaliplatin (l-OHP) were entrapped in alginate bead... more Folic Acid conjugated liposomes encapsulating Oxaliplatin (l-OHP) were entrapped in alginate beads and further coated with Eudragit-S-100 for effective delivery to colon tumors. Liposomes were prepared by cast film method and folic acid was coupled on the surface of liposomes. They were further entrapped in alginate beads which were Eudragit coated for degradation in the colonic region. The prepared beads were characterized for shape and surface morphology, percentage entrapment efficiency and drug release studies. The in vitro drug release was investigated using a USP dissolution paddle type apparatus in different simulated gastrointestinal fluids. In vivo studies of the beads containing free drug, folic acid coupled and uncoupled liposomes bearing l-OHP was administered orally at the dose of 10mg l-OHP/kg body weight to tumor bearing NUDE/SCID mice. γ-Scintigraphic study showed that Eudragit coated alginate beads entered into the colon of Balb/c mice between 4.20 and 4.50h after o...
Indian journal of clinical biochemistry : IJCB, 2010
The present study was carried out in the Sahariya tribe of Central India, which reportedly have h... more The present study was carried out in the Sahariya tribe of Central India, which reportedly have high prevalence of pulmonary tuberculosis. Total serum LDH and its tissue specific isoforms were estimated in TB patients and matched healthy controls to test the utility of LDH as diagnostic marker for tuberculosis. About 210 sputum positive cases and 328 age and sex matched sputum negative controls were recruited. The spectrophotometeric and densitometric analysis of each LDH isoform was carried out in both cases and controls. The mean values of serum LDH were estimated and compared for each class by t-test. The statistical comparisons were made between sputum negative controls and sputum positive cases by Mann-Whitney's U test. The spectrophotometric estimation of serum LDH revealed significant (P=0.0016) increase in its level in cases (290 IU/L) as compared to controls (248 IU/L). The densitometric analysis of individual LDH isoforms in cases and controls demonstrated significant ...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
Latent tuberculosis infection affects one third of the world's population and can reactivate ... more Latent tuberculosis infection affects one third of the world's population and can reactivate (relapse) decades later. However, current technologies, dependent on postmortem analyses, cannot follow the temporal evolution of disease. C3HeB/FeJ mice, which develop necrotic and hypoxic tuberculosis lesions, were aerosol-infected with Mycobacterium tuberculosis. PET and CT were used to serially image the same cohort of infected mice through pretreatment, tuberculosis treatment, and subsequent development of relapse. A novel diffeomorphic registration was successfully used to monitor the spatial evolution of individual pulmonary lesions. Although most lesions during relapse developed in the same regions as those noted during pretreatment, several lesions also arose de novo within regions with no prior lesions. This study presents a novel model that simulates infection and reactivation disease as seen in humans and could prove valuable to study tuberculosis pathogenesis and evaluate no...
The presence of cavitary lesions in patients with tuberculosis poses a significant clinical conce... more The presence of cavitary lesions in patients with tuberculosis poses a significant clinical concern due to the risk of infectivity and the risk of antibiotic treatment failure. We describe 2 algorithms that use noninvasive positron emission tomography (PET) and computed tomography (CT) to predict the development of cavitary lesions in rabbits. Analysis of the PET region of interest predicted cavitary disease with 100% sensitivity and 76% specificity, and analysis of the CT region of interest predicted cavitary disease with 83.3% sensitivity and 76.9% specificity. Our results show that restricting our analysis to regions with high [(18)F]-fluorodeoxyglucose uptake provided the best combination of sensitivity and specificity.
2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009
Many techniques have been proposed to segment organs from images, however the segmentation of dis... more Many techniques have been proposed to segment organs from images, however the segmentation of diseased organs remains challenging and frequently requires lots of user interaction. The challenge consists of segmenting an organ while its appearance and its shape vary due to the presence of the disease in addition to individual variations. We propose a template registration technique that can be used to recover the complete segmentation of a diseased organ from a partial segmentation. The usual template registration method is modified in such a way that it is robust to missing parts. The proposed method is used to segment Mycobacterium tuberculosis infected lungs in CT images of experimentally infected mice. Using synthetic data, we evaluate and compare the performance of the proposed algorithm with the usual sum of squared difference cost function.
Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible l... more Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP-1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human-like cavities (100% by day 28), with resultant bacillary burdens (>10(7) CFU/g) far greater than those found in matched granulomatous tissue (10(5) CFU/g). Using a novel, breath-hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by changes in lung density during controlled pulmonary expansion (R(2) = 0.6356, p…
ABSTRACT PURPOSE To develop a complete image analysis and quantification framework that accuratel... more ABSTRACT PURPOSE To develop a complete image analysis and quantification framework that accurately determines disease severity and its progression in pulmonary infections using three small animal models—rabbit, ferret, and mouse. METHOD AND MATERIALS We designed a fast and robust automated image analysis platform with a quantification tool that facilitates accurate quantification of pulmonary lesions, and an image registration pipeline that supports a volumetric comparison of all serial scans using PET and CT images. The proposed method for analysis contained three steps: (i) the lung was segmented via an interactive region growing method (ii) mathematical morphology was then applied to this binary mask to remove all non-lung regions from the images; and (iii) then the affinity propagation based clustering algorithm was used on all PET images to precisely segment the high uptake regions. The proposed framework was tested using sequentially acquired CT and PET images. The rabbits were infected with Mycobacterium tuberculosis (TB) (92 PET-CT scans). The ferrets were injected with the H1N1 influenza virus (44 PET-CT scans), and the mice were infected with an aerosolized respiratory pathogen (24 PET-CT scans). Segmentations were evaluated by expert radiologists and compared with ground truth segmentations. RESULTS Each small animal model was evaluated within the same animal type and the Dice Similarity Coefficient (DSC), and the Haussdorf distance (HD) were used for evaluation of the proposed method. The estimated lesion volume sizes from CT and PET images, estimated from the proposed method and the ground truth (R2=0.8922, p<0.01 and R2=0.8664, p<0.01, respectively), were significant. The DSC(%) was 93.4±4.5% for normal lung CT scans and 86.0±7.1% for pathological lung CT scans. Similarly, a DSC of 89.06±9.83% was obtained for PET images. Experiments showed excellent agreements (all above 85%), with expert evaluations for both structural and functional imaging modalities. CONCLUSION The proposed computational framework can increase the efficiency and quality of pre-clinical findings relative to clinical standards and decrease the inter-observer variation from manual quantification methods that can obscure findings. CLINICAL RELEVANCE/APPLICATION This framework can be applied clinically for accurate, efficicent, and robust quantification of infectious diseases using longitudinal PET-CT images.
ABSTRACT PURPOSE To develop a novel segmentation method that can identify and quantify diffuse an... more ABSTRACT PURPOSE To develop a novel segmentation method that can identify and quantify diffuse and multi-focal uptake regions using small animal model PET images that have a diagnosis of a pulmonary infection. METHOD AND MATERIALS Our segmentation approach is based on affinity propagation (AP) clustering and uses a novel distance metric and a probability density function that is estimated from a smoothed histogram. An overview of the proposed method is as follows: (i) the PET image histogram was estimated and smoothed by using a diffusion based kernel density estimation, (ii) a novel similarity function was constructed to determine how similar the histogram data points are to each other, based on two constraints: probability based and intensity based constraints, with the assumption that points that are more similar are more likely to belong to the same classification, and (iii) the AP clustering was applied to the similarities between the data points in order to find optimal thresholding levels that can separate the significant uptake regions into several tissue labels. Our proposed method was tested using an infectious disease small animal model that consisted of imaging ten rabbits at weeks 0,5,10,15,20,30, and 38 with FDG-PET—and all rabbits were infected with an aerosolized Mycobacterium Tuberculosis. Two experts segmented the images to define the ground truth for comparison. RESULTS The Dice Similarity Coefficient (DSC) and the sensitivity and specificity were calculated between the segmentation regions that were found by the proposed method and then compared to expert delineations. An average DSC of 89.06±9.82% with a sensitivity of 97.87±7.09% and a specificity of 83.70±15.32% were achieved. The Pearson correlation coefficient between the delineation performances of the two expert observers was R2=0.85 (p<0.01), while the correlation coefficient between the proposed method and the average of the observers segmentations was R2=0.91 (p<0.01). CONCLUSION Current PET segmentation techniques focus on focal uptake regions and are not well suited for multi-focal uptake regions, commonly found in infectious lung diseases. Our proposed segmentation method quantified the multi-focal uptake regions with high accuracy and within seconds—and it outperformed the state-of-the-art methods. CLINICAL RELEVANCE/APPLICATION This method can be used to segment diffuse and multi-focal FDG uptake normally seen in PET images from patients with infectious diseases like TB.
International journal of biological macromolecules, Jan 13, 2015
Folic Acid conjugated liposomes encapsulating Oxaliplatin (l-OHP) were entrapped in alginate bead... more Folic Acid conjugated liposomes encapsulating Oxaliplatin (l-OHP) were entrapped in alginate beads and further coated with Eudragit-S-100 for effective delivery to colon tumors. Liposomes were prepared by cast film method and folic acid was coupled on the surface of liposomes. They were further entrapped in alginate beads which were Eudragit coated for degradation in the colonic region. The prepared beads were characterized for shape and surface morphology, percentage entrapment efficiency and drug release studies. The in vitro drug release was investigated using a USP dissolution paddle type apparatus in different simulated gastrointestinal fluids. In vivo studies of the beads containing free drug, folic acid coupled and uncoupled liposomes bearing l-OHP was administered orally at the dose of 10mg l-OHP/kg body weight to tumor bearing NUDE/SCID mice. γ-Scintigraphic study showed that Eudragit coated alginate beads entered into the colon of Balb/c mice between 4.20 and 4.50h after o...
Indian journal of clinical biochemistry : IJCB, 2010
The present study was carried out in the Sahariya tribe of Central India, which reportedly have h... more The present study was carried out in the Sahariya tribe of Central India, which reportedly have high prevalence of pulmonary tuberculosis. Total serum LDH and its tissue specific isoforms were estimated in TB patients and matched healthy controls to test the utility of LDH as diagnostic marker for tuberculosis. About 210 sputum positive cases and 328 age and sex matched sputum negative controls were recruited. The spectrophotometeric and densitometric analysis of each LDH isoform was carried out in both cases and controls. The mean values of serum LDH were estimated and compared for each class by t-test. The statistical comparisons were made between sputum negative controls and sputum positive cases by Mann-Whitney's U test. The spectrophotometric estimation of serum LDH revealed significant (P=0.0016) increase in its level in cases (290 IU/L) as compared to controls (248 IU/L). The densitometric analysis of individual LDH isoforms in cases and controls demonstrated significant ...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014
Latent tuberculosis infection affects one third of the world's population and can reactivate ... more Latent tuberculosis infection affects one third of the world's population and can reactivate (relapse) decades later. However, current technologies, dependent on postmortem analyses, cannot follow the temporal evolution of disease. C3HeB/FeJ mice, which develop necrotic and hypoxic tuberculosis lesions, were aerosol-infected with Mycobacterium tuberculosis. PET and CT were used to serially image the same cohort of infected mice through pretreatment, tuberculosis treatment, and subsequent development of relapse. A novel diffeomorphic registration was successfully used to monitor the spatial evolution of individual pulmonary lesions. Although most lesions during relapse developed in the same regions as those noted during pretreatment, several lesions also arose de novo within regions with no prior lesions. This study presents a novel model that simulates infection and reactivation disease as seen in humans and could prove valuable to study tuberculosis pathogenesis and evaluate no...
The presence of cavitary lesions in patients with tuberculosis poses a significant clinical conce... more The presence of cavitary lesions in patients with tuberculosis poses a significant clinical concern due to the risk of infectivity and the risk of antibiotic treatment failure. We describe 2 algorithms that use noninvasive positron emission tomography (PET) and computed tomography (CT) to predict the development of cavitary lesions in rabbits. Analysis of the PET region of interest predicted cavitary disease with 100% sensitivity and 76% specificity, and analysis of the CT region of interest predicted cavitary disease with 83.3% sensitivity and 76.9% specificity. Our results show that restricting our analysis to regions with high [(18)F]-fluorodeoxyglucose uptake provided the best combination of sensitivity and specificity.
2009 IEEE International Symposium on Biomedical Imaging: From Nano to Macro, 2009
Many techniques have been proposed to segment organs from images, however the segmentation of dis... more Many techniques have been proposed to segment organs from images, however the segmentation of diseased organs remains challenging and frequently requires lots of user interaction. The challenge consists of segmenting an organ while its appearance and its shape vary due to the presence of the disease in addition to individual variations. We propose a template registration technique that can be used to recover the complete segmentation of a diseased organ from a partial segmentation. The usual template registration method is modified in such a way that it is robust to missing parts. The proposed method is used to segment Mycobacterium tuberculosis infected lungs in CT images of experimentally infected mice. Using synthetic data, we evaluate and compare the performance of the proposed algorithm with the usual sum of squared difference cost function.
Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible l... more Active tuberculosis (TB) often presents with advanced pulmonary disease, including irreversible lung damage and cavities. Cavitary pathology contributes to antibiotic failure, transmission, morbidity and mortality. Matrix metalloproteinases (MMPs), in particular MMP-1, are implicated in TB pathogenesis. We explored the mechanisms relating MMP/TIMP imbalance to cavity formation in a modified rabbit model of cavitary TB. Our model resulted in consistent progression of consolidation to human-like cavities (100% by day 28), with resultant bacillary burdens (>10(7) CFU/g) far greater than those found in matched granulomatous tissue (10(5) CFU/g). Using a novel, breath-hold computed tomography (CT) scanning and image analysis protocol, we showed that cavities developed rapidly from areas of densely consolidated tissue. Radiological change correlated with a decrease in functional lung tissue, as estimated by changes in lung density during controlled pulmonary expansion (R(2) = 0.6356, p…
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