Total-liver-volume perfusion CT using 3-D image fusion to improve detection and characterization of liver metastases

The purpose of this study was to evaluate the feasibility of a totalliver- volume perfusion CT (CTP) technique for the detection and characterization of livermetastases. Twenty patients underwent helical CT of the total liver volume before and 11 times after intravenous contrast-material injection. To decrease distortion artifacts, all phases were co-registered using 3-D image fusion before creating blood-flow maps. Lesion-based sensitivity and specificity for liver metastases of first the conventional four phases (unenhanced, arterial, portal venous, and equilibrium) and later all 12 phases including blood-flow maps were determined as compared to intraoperative ultrasound and surgical exploration. Arterial and portal venous perfusion was calculated for normalappearing and metastatic liver tissue. Total-liver-volume perfusion values were comparable to studies using single-level CTP. Compared to fourphase CT, total -liver-volume CTP increased sensitivity to 89.2 from 78.4% (P=0.046) and specificity to 82.6 from 78.3% (P=0.074). Total - liver-volume CTP is a noninvasive, quantitative, and feasible technique. Preliminary results suggest an improved detection of liver metastases for CTP compared to four-phase CT

Evaluation of Hepatocellular Carcinoma Transarterial Chemoembolization using Quantitative Analysis of 2D and 3D Real-time Contrast Enhanced Ultrasound.

Quantitative 2D and 3D contrast-enhanced ultrasound (CEUS) was assessed to evaluate early transarterial chemoembolization (TACE) treatment response. Seventeen patients scheduled for TACE for the treatment of hepatocellular carcinoma participated in the study. 2D and 3D CEUS were performed for each patient at three time points: Prior to TACE, 1-2 weeks post TACE, and 1 month post TACE. Peak-intensities of the tumor and surrounding liver tissue were calculated from 2D and 3D data before and after TACE and used to evaluate tumor treatment response. Residual tumor percentages were calculated from 2D and 3D CEUS acquired 1-2 weeks and 1 month post TACE and compared with results from MRI 1 month post TACE. Nine subjects had complete response while 8 had incomplete response. Peak-intensities of the tumor from 3D CEUS prior to TACE were similar between the complete and incomplete treatment groups (p = 0.70), while 1-2 weeks (p \u3c 0.01) and 1 month post treatment (p \u3c 0.01) were significantly lower in the complete treatment group than in the incomplete treatment group. For 2D CEUS, only the peak-intensity values of the tumor from 1 month post TACE were significantly different (p \u3c 0.01). The correlation coefficients between 2D and 3D residual tumor estimates 1-2 weeks post TACE and the estimates from MRI were 0.73 and 0.94, respectively, while those from 2D and 3D CEUS 1 month post TACE were 0.66 and 0.91, respectively. Quantitative analysis on 2D and 3D CEUS shows potential to differentiate patients with complete versus incomplete response to TACE as early as 1-2 weeks post treatment

Quantitative analysis of the perfusion in the kidneys, liver, pancreas, small intestine and mesenteric lymph nodes in healthy cats using contrast enhanced ultrasound

Peer reviewe

EVALUATION OF LIVER PARENCHYMA AND PERFUSION USING DYNAMIC CONTRAST-ENHANCED COMPUTED TOMOGRAPHY AND CONTRAST-ENHANCED ULTRASONOGRAPHY IN CAPTIVE GREEN IGUANAS (IGUANA IGUANA) UNDER GENERAL ANESTHESIA

Background: Contrast-enhanced diagnostic imaging techniques are considered useful in veterinary and human medicine to evaluate liver perfusion and focal hepatic lesions. Although hepatic diseases are a common occurrence in reptile medicine, there is no reference to the use of contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) to evaluate the liver in lizards. Therefore, the aim of this study was to evaluate the pattern of change in echogenicity and attenuation of the liver in green iguanas (Iguana iguana) after administration of specific contrast media. Results: An increase in liver echogenicity and density was evident during CEUS and CECT, respectively. In CEUS, the mean \ub1 SD (median; range) peak enhancement was 19.9% \ub1 7.5 (18.3; 11.7-34.6). Time to peak enhancement was 134.0 \ub1 125.1 (68.4; 59.6-364.5) seconds. During CECT, first visualization of the contrast medium was at 3.6 \ub1 0.5 (4; 3-4) seconds in the aorta, 10.7 \ub1 2.2 (10.5; 7-14) seconds in the hepatic arteries, and 15 \ub1 4.5 (14.5; 10-24) seconds in the liver parenchyma. Time to peak was 14.1 \ub1 3.4 (13; 11-21) and 31 \ub1 9.6 (29; 23-45) seconds in the aorta and the liver parenchyma, respectively. Conclusion: CEUS and dynamic CECT are practical means to determine liver hemodynamics in green iguanas. Distribution of contrast medium in iguana differed from mammals. Specific reference ranges of hepatic perfusion for diagnostic evaluation of the liver in iguanas are necessary since the use of mammalian references may lead the clinician to formulate incorrect diagnostic suspicions

Dynamic Contrast Enhanced Computed Tomography Measurement of Perfusion in Hepatic Cancer

ABSTRACT In recent years, the incidence and mortality rate for hepatocellular carcinoma (HCC) have increased due to the emergence of hepatitis B, C and other diseases that cause cirrhosis. The progression from cirrhosis to HCC is characterized by abnormal vascularization and by a shift from a venous to an arterial blood supply. A knowledge of HCC vascularity which is manifested as alterations in liver blood flow may distinguish among different stages of liver disease and can be used to monitor response to treatment. Unfortunately, conventional diagnostic imaging techniques lack the ability to accurately quantify HCC vascularity. The purpose of this thesis was to validate and assess the diagnostic capabilities of dynamic contrast enhanced computed tomography (DCE-CT) and perfusion software designed to measure hepatic perfusion. Chapter 2 described a study designed to evaluate the accuracy and precision of hepatic perfusion measurement. The results showed a strong correlation between hepatic artery blood flow measurement with DCE-CT and radioactive microspheres under steady state in a rabbit model for HCC (VX2 carcinoma). Using repeated measurements and Monte Carlo simulations, DCE-CT perfusion measurements were found to be precise; with the highest precision in the tumor rim. In Chapter 3, we used fluorine-18 fluoro-2-deoxy-D-glucose (FDG) positron emission tomography and DCE-CT perfusion to determined an inverse correlation between glucose utilization and tumor blood flow; with an R of 0.727 (P \u3c 0.05). This suggests a limited supply of oxygen (possibly hypoxia) and that the tumor cells were surviving via anaerobic glycolysis. in In Chapter 4, hepatic perfusion data showed that thalidomide caused a reduction of tumor perfusion in the responder group during the first 8 days after therapy, P \u3c 0.05; while perfusion in the partial responder and control group remained unchanged, P \u3e 0.05. These changes were attributed to vascular remodeling and maturation resulting in a more functional network of endothelial tubes lined with pericytes. The results of this thesis demonstrate the accuracy and precision of DCE-CT hepatic perfusion measurements. It also showed that DCE-CT perfusion has the potential to enhance the functional imaging ability of hybrid PET/CT scanners and evaluate the efficacy of anti-angiogenesis therapy

Perfusion computed tomography of the liver

Background: Perfusion CT (P-CT) is a relatively new imaging technique that permits the visual and quantitative assessment of the micro- and macrocirculation of a target organ and focal lesions. P-CT has shown promising results in the evaluation of hyper-vascular tumors such as hepatocellular carcinoma (HCC). HCC is the sixth most common cancer globally and it has a poor prognosis when discovered at a late tumor stage. Any improvement in HCC detection would be directly beneficial for patient care. This thesis aims to investigate the strengths and limitations of whole liver P-CT and to evaluate if PCT can improve the detection of hyper-vascular liver lesions in patients with chronic liver disease. Methods: Study I: Twenty-four patients, who underwent dynamic P-CT for detection of HCC were retrospectively divided into three groups: (1) without portal-venous hypertension (PVH) (n = 8), (2) with PVH (n = 8), (3) with PVH and thrombosis (n = 8). Time to peak splenic- and peak renal enhancement (PSE resp. PRE), as well as arterial liver perfusion (ALP), portal- venous liver perfusion (PLP) and hepatic perfusion-index (HPI) of the liver and HCC derived from PSE- versus PRE- based modelling were compared between the groups. Study II: Group A (n=15) and Group B (n= 38) underwent P-CT using 50 ml contrast medium (CM). Group B underwent an additional standard multiphasic liver CT using 120ml (70-143 ml). Triple-arterial CT image sets were reconstructed from P-CT by fusing three dedicated arterial time points. Triple-arterial CT and single-arterial CT were compared by two readers (R1, R2), who assessed subjective image quality (IQ) and HCC detection rate. A third reader assessed objective IQ.Study III: Fifty study participants (Group A) were scanned with P-CT, a high CM volume protocol and bolus-tracking technique to depict ten arterial phases. Time attenuation curves were created for hyper-vascular liver lesions, liver parenchyma and hepatic vascular structures. 16 participants of Group A with lesions were further analyzed and radiation dose-neutral quadruple arterial phase image sets were created (Group A1). Group A1 was then compared to a Control Group (Group B) consisting of 16 consecutive patients undergoing standard single arterial phase scans. Lesion depiction and quantitative IQ were compared. Results: Study I: Time to PSE was significantly delayed in PVH groups 2 and 3 (P = 0.02), whereas PRE was similar in groups 1, 2 and 3 (P > 0.05). In group 1, liver and HCC perfusion parameters were similar for PSE- and PRE-based modelling (all P > 0.05), while significant differences were seen for PLP and HPI (liver only) in group 2 and ALP in group 3 (all P < 0.05). Study II: The mean CTDIvol of triple-arterial CT and single-arterial CT was equivalent (P=0.73). Triple-arterial CT showed lower image noise and better contrast-to-noise-ratio (P<0.001, P=0.032, respectively), but no significant difference in lesion-to-liver-contrast-ratio (P=0.31). Subjective IQ was good for both protocols. The detection rate of the 65 HCC lesions was 82%/83% (R1/R2) at triple-arterial CT and 80%/77% (R1/R2) at single-arterial CT (P=0.4). Study III: Both Group A1 and B had 33 hyper-enhancing liver lesions each. The mean CTDIvol of quadruple-arterial CT and single-arterial CT was equivalent (P=0.16). The mean time to reach peak lesion-to-liver contrast (LLC) was 20.1s (±4.2s) with a range of 12.5s to 29.1s. Quadruple arterial CT performed significantly better than the Control Group in regards to LLC (P= .009), CNR (P= .002), Image Noise (P<0.001) and hepatic artery enhancement(P<0.001). Conclusions: Study I: PSE is significantly delayed in patients with portal venous hypertension, which results in a miscalculation of P-CT parameters. Maximum-slope based P-CT could be improved by replacing the spleen with the kidney as the reference organ. The difference between time to PSE and time to PRE might serve as a non-invasive biomarker of portal venous hypertension. Study II: Radiation dose-equivalent triple arterial phase imaging is feasible and showed superior image quality and similar HCC detection rate as standard single arterial phase CT despite a substantially smaller CM volume. Study III: The optimal scan delay at single arterial phase CT for depiction of hyper-vascular liver lesions occurs at 20 s, when using a high iodine dose CM protocol and bolus-tracking. Fused quadruple arterial phase CT significantly increases lesion depiction, quantitative IQ and hepatic artery enhancement as compared to standard single arterial phase CT, without elevating the total radiation dose

CT PERFUSION INVESTIGATION OF HEPATIC HEMODYNAMICS IN A RODENT MODEL OF LIVER CIRRHOSIS

This thesis aims to evaluate the utility of dynamic contrast enhanced computed tomography (DCE-CT) imaging in conjunction with kinetic analysis (CT Perfusion) for the investigation of fibrotic liver disease. Monte Carlo simulations and sensitivity analysis of the kinetic model were used to characterize the bias, variance and covariance of perfusion parameters calculated with CT Perfusion. DCE-CT scans were performed on rats treated with carbon tetrachloride (CCI4) for 8 weeks to induce liver fibrosis, as well as sham injected control rats. Perfusion parameters were then derived from the DCE-CT scans using CT Perfusion. CCI4 treated rats showed significant changes in total hepatic blood flow, arterial hepatic blood flow, blood volume, and arterial fraction of blood flow. Histological samples were collected at various stages of treatment and stained with methyl blue. Digital image analysis was used to quantify fibrosis content of stained tissue. A strong correlation was found between fibrosis content and arterial fraction of blood flow (r=.82 p\u3c.00001)