Side-effect of chemotherapy on liver in lymphoma patients studied by standard uptake value.

The aim of this thesis study is to ascertain if there are changes in F-18 FDG uptake in the liver after chemotherapy R-CHOP in patients having diffuse large B-cell non-Hodgkin’s lymphoma. PET using 18 F-FDG is used to detect enhanced glycolysis in cancer cells and has proven to be valuable in diagnosis, staging and assessing response to therapy in a multitude of malignant disorder. PET/CT images of 19 patients both male and female, aged between 48 to 80 years was analyzed in the present study. PET/CT scan of the patients were taken one week before, one week after, one month after and four months after chemotherapy. The images in all these cases were analyzed for changes in F-18 FDG uptake in liver before the treatment with R-CHOP and in different period after treatment. The changes were quantified by means of standard uptake value. The changes in standard uptake value were also compared with changes in liver function test before and one month after chemotherapy. The present study demonstrates there are changes in alanine aminotransferase, alkaline phosphatase and mean 18 F-FDG uptake in liver by R-CHOP chemotherapy in patients with diffuse large B-cell Non-Hodgkin’s lymphoma. However, the decrease in ALT and AFOS value was not significant one month after chemotherapy

Side-effect of chemotherapy on liver in lymphoma patients studied by standard uptake value.

The aim of this thesis study is to ascertain if there are changes in F-18 FDG uptake in the liver after chemotherapy R-CHOP in patients having diffuse large B-cell non-Hodgkin’s lymphoma. PET using 18 F-FDG is used to detect enhanced glycolysis in cancer cells and has proven to be valuable in diagnosis, staging and assessing response to therapy in a multitude of malignant disorder. PET/CT images of 19 patients both male and female, aged between 48 to 80 years was analyzed in the present study. PET/CT scan of the patients were taken one week before, one week after, one month after and four months after chemotherapy. The images in all these cases were analyzed for changes in F-18 FDG uptake in liver before the treatment with R-CHOP and in different period after treatment. The changes were quantified by means of standard uptake value. The changes in standard uptake value were also compared with changes in liver function test before and one month after chemotherapy. The present study demonstrates there are changes in alanine aminotransferase, alkaline phosphatase and mean 18 F-FDG uptake in liver by R-CHOP chemotherapy in patients with diffuse large B-cell Non-Hodgkin’s lymphoma. However, the decrease in ALT and AFOS value was not significant one month after chemotherapy

Effects of human articular cartilage constituents on simultaneous diffusion of cationic and nonionic contrast agents

Contrast‐enhanced computed tomography is an emerging diagnostic technique for osteoarthritis. However, the effects of increased water content, as well as decreased collagen and proteoglycan concentrations due to cartilage degeneration, on the diffusion of cationic and nonionic agents, are not fully understood. We hypothesize that for a cationic agent, these variations increase the diffusion rate while decreasing partition, whereas, for a nonionic agent, these changes increase both the rate of diffusion and partition. Thus, we examine the diffusion of cationic and nonionic contrast agents within degraded tissue in time‐ and depth‐dependent manners. Osteochondral plugs (N = 15,\ua0d = 8 mm) were extracted from human cadaver knee joints, immersed in a mixture of cationic CA4+ and nonionic gadoteridol contrast agents, and imaged at multiple time‐points, using the dual‐contrast method. Water content, and collagen and proteoglycan concentrations were determined using lyophilization, infrared spectroscopy, and digital densitometry, respectively. Superficial to mid (0%‐60% depth) cartilage CA4+ partitions correlated with water content (R

Effects of human articular cartilage constituents on simultaneous diffusion of cationic and nonionic contrast agents

Contrast-enhanced computed tomography is an emerging diagnostic technique for osteoarthritis. However, the effects of increased water content, as well as decreased collagen and proteoglycan concentrations due to cartilage degeneration, on the diffusion of cationic and nonionic agents, are not fully understood. We hypothesize that for a cationic agent, these variations increase the diffusion rate while decreasing partition, whereas, for a nonionic agent, these changes increase both the rate of diffusion and partition. Thus, we examine the diffusion of cationic and nonionic contrast agents within degraded tissue in time- and depth-dependent manners. Osteochondral plugs (N = 15, d = 8 mm) were extracted from human cadaver knee joints, immersed in a mixture of cationic CA4+ and nonionic gadoteridol contrast agents, and imaged at multiple time-points, using the dual-contrast method. Water content, and collagen and proteoglycan concentrations were determined using lyophilization, infrared spectroscopy, and digital densitometry, respectively. Superficial to mid (0%-60% depth) cartilage CA4+ partitions correlated with water content (R < −0.521, P <.05), whereas in deeper (40%-100%) cartilage, CA4+ correlated only with proteoglycans (R > 0.671, P <.01). Gadoteridol partition correlated inversely with collagen concentration (0%-100%, R < −0.514, P <.05). Cartilage degeneration substantially increased the time for CA4+ compared with healthy tissue (248 ± 171 vs 175 ± 95 minute) to reach the bone-cartilage interface, whereas for gadoteridol the time (111 ± 63 vs 179 ± 163 minute) decreased. The work clarifies the diffusion mechanisms of two different contrast agents and presents depth and time-dependent effects resulting from articular cartilage constituents. The results will inform the development of new contrast agents and optimal timing between agent administration and joint imaging.Biomaterials & Tissue Biomechanic

Imaging of proteoglycan and water contents in human articular cartilage with full-body CT using dual contrast technique

Assessment of cartilage composition via tomographic imaging is critical after cartilage injury to prevent post-traumatic osteoarthritis. Diffusion of cationic contrast agents in cartilage is affected by proteoglycan loss and elevated water content. These changes have opposite effects on diffusion and, thereby, reduce the diagnostic accuracy of cationic agents. Here, we apply, for the first time, a clinical full-body CT for dual contrast imaging of articular cartilage. We hypothesize that full-body CT can simultaneously determine the diffusion and partitioning of cationic and non-ionic contrast agents and that normalization of the cationic agent partition with that of the non-ionic agent minimizes the effect of water content and tissue permeability, especially at early diffusion time points. Cylindrical (d = 8 mm) human osteochondral samples (n = 45; four cadavers) of a variable degenerative state were immersed in a mixture of cationic iodinated CA4+ and non-charged gadoteridol contrast agents and imaged with a full-body CT scanner at various time points. Determination of contrast agents’ distributions within cartilage was possible at all phases of diffusion. At early time points, gadoteridol, and CA4+ distributed throughout cartilage with lower concentrations in the deep cartilage. At ≥24 h, the gadoteridol concentration remained nearly constant, while the CA4+ concentration increased toward deep cartilage. Normalization of the CA4+ partition with that of gadoteridol significantly (p < 0.05) enhanced correlation with proteoglycan content and Mankin score at the early time points. To conclude, the dual contrast technique was found advantageous over single contrast imaging enabling more sensitive diagnosis of cartilage degeneration

Quantitative dual contrast CT technique for evaluation of articular cartilage properties

Impact injuries\ua0of cartilage may initiate post-traumatic degeneration, making early detection of injury imperative for timely surgical or pharmaceutical interventions. Cationic (positively-charged) CT contrast agents detect loss of cartilage proteoglycans (PGs) more sensitively than anionic (negatively-charged) or non-ionic (non-charged, i.e., electrically neutral) agents. However, degeneration related loss of PGs and increase in water content have opposite effects on the diffusion of the cationic agent, lowering its sensitivity. In contrast to cationic agents, diffusion of non-ionic agents is governed only by steric hindrance and water content\ua0of cartilage. We hypothesize that sensitivity of\ua0an iodine(I)-based cationic agent may be enhanced by simultaneous use of a non-ionic gadolinium(Gd)-based agent. We introduce a quantitative dual energy CT technique (QDECT) for simultaneous quantification of two contrast agents in cartilage. We employ this technique to improve the sensitivity of cationic CA4+ (q =+4) by normalizing its partition in cartilage with that of non-ionic gadoteridol. The technique was evaluated with measurements of contrast agent mixtures of known composition and human osteochondral samples (n = 57) after immersion (72\ua0h) in mixture of CA4+ and gadoteridol. Samples were arthroscopically graded and biomechanically tested prior to QDECT (50/100\ua0kV). QDECT determined contrast agent mixture compositions correlated with the true compositions (R = 0.99, average error = 2.27%). Normalizing CA4+ partition in cartilage with that of gadoteridol improved correlation with equilibrium modulus (from ρ = 0.701 to 0.795). To conclude, QDECT enables simultaneous quantification of I and Gd contrast agents improving diagnosis of cartilage integrity and biomechanical status

Dual contrast in computed tomography allows earlier characterization of articular cartilage over single contrast

Cationic computed tomography contrast agents are more sensitive for detecting cartilage degeneration than anionic or non-ionic agents. However, osteoarthritis-related loss of proteoglycans and increase in water content contrarily affect the diffusion of cationic contrast agents, limiting their sensitivity. The quantitative dual-energy computed tomography technique allows the simultaneous determination of the partitions of iodine-based cationic (CA4+) and gadolinium-based non-ionic (gadoteridol) agents in cartilage at diffusion equilibrium. Normalizing the cationic agent partition at diffusion equilibrium with that of the non-ionic agent improves diagnostic sensitivity. We hypothesize that this sensitivity improvement is also prominent during early diffusion time points and that the technique is applicable during contrast agent diffusion. To investigate the validity of this hypothesis, osteochondral plugs (d = 8 mm, N = 33), extracted from human cadaver (n = 4) knee joints, were immersed in a contrast agent bath (a mixture of CA4+ and gadoteridol) and imaged using the technique at multiple time points until diffusion equilibrium. Biomechanical testing and histological analysis were conducted for reference. Quantitative dual-energy computed tomography technique enabled earlier determination of cartilage proteoglycan content over single contrast. The correlation coefficient between human articular cartilage proteoglycan content and CA4+ partition increased with the contrast agent diffusion time. Gadoteridol normalized CA4+ partition correlated significantly (P &lt;.05) with Mankin score at all time points and with proteoglycan content after 4 hours. The technique is applicable during diffusion, and normalization with gadoteridol partition improves the sensitivity of the CA4+ contrast agent.Biomaterials & Tissue Biomechanic