Hepatic Blood Volume Research Articles

Imaging and Quantification of the Hepatic Vasculature of Mice Using Ultrafast Doppler Ultrasound.

Non-invasive in vivo imaging of the vasculature is a powerful tool for studying disease mechanisms in rodents. To achieve high sensitivity imaging of the microvasculature using Doppler ultrasound methods, imaging modalities employing the concept of ultrafast imaging are preferred. By increasing the frame rate of the ultrasound scanner to thousands of frames per second, it becomes possible to improve the sensitivity of the blood flow down to 2 mm/s and to obtain functional information about the microcirculation in comparison to a sensitivity of around 1 cm/s in conventional Doppler modes. While Ultrafast Doppler ultrasound (UFUS) imaging has become adopted in neuroscience, where it can capture brain activity through neurovascular coupling, it presents greater challenges when imaging the vasculature of abdominal organs due to larger motions linked to breathing. The liver, positioned anatomically under the diaphragm, is particularly susceptible to out-of-plane movement and oscillating respiratory motion. These artifacts not only adversely affect Doppler imaging but also complicate the anatomical analysis of vascular structures and the computation of vascular parameters. Here, we present a qualitative and quantitative imaging analysis of the hepatic vasculature in mice by UFUS. We identify major anatomical vascular structures and provide graphical illustrations of the hepatic macroscopical anatomy, comparing it to an in-depth anatomical assessment of the hepatic vasculature based on Doppler readouts. Additionally, we have developed a quantification protocol for robust measurements of hepatic blood volume of the microvasculature over time. To contemplate further research, qualitative vascular analysis provides a comprehensive overview and suggests a standardized terminology for researchers working with mouse models of liver disease. Furthermore, it offers the opportunity to apply ultrasound as a non-invasive complementary method to inspect hepatic vascular defects in vivo and measure functional microvascular alterations deep within the organ before unraveling blood vessel anomalies at the micron scale levels using ex vivo staining on tissue sections.

Hepatic blood volume is decreased in patients with cirrhosis and does not decrease further after a meal like in healthy persons

Background & Aims The aim was to measure fractional hepatic blood volume (HBV) and hepatic blood flow (HBF) before and after a meal in patients with cirrhosis (n = 7) and healthy persons (n = 6). Methods Catheters were placed in a radial artery and a hepatic vein for blood sampling and a peripheral vein for indocyanine green (ICG) infusion. A 6-min positron emission tomography (PET) liver scan was performed after inhalation of 1000 MBq 15O-CO and repeated after ingestion of a standard meal. HBV was calculated as the 15O-CO concentration in liver tissue (PET) divided by that in arterial blood. HBF was calculated from ICG infusion rate and arterial and hepatic venous blood concentrations according to Fick’s principle. Results Mean fasting HBV was 14 mL blood/100 mL liver tissue in patients with cirrhosis and 21 mL blood/100 mL liver tissue in healthy subjects (p < .01). Mean HBV did not change postprandially in patients with cirrhosis (13 mL blood/100 mL liver tissue) but decreased in healthy subjects (17 mL blood/100 mL liver tissue; p = .02). Mean fasting HBF was 1.5 L blood/min in patients with cirrhosis and 1.1 L blood/min in healthy subjects and increased in both groups of subjects to 1.8 L blood/min. Conclusions Fasting HBV was lower in patients with cirrhosis and did not decrease postprandially as it did in the healthy controls although the HBF increased equally. Patients with cirrhosis thus have a disturbed hemodynamic response to normo-physiological changes such as a meal.

Improved Visualization of the Necrotic Zone after Microwave Ablation Using Computed Tomography Volume Perfusion in an In Vivo Porcine Model

After hepatic microwave ablation, the differentiation between fully necrotic and persistent vital tissue through contrast enhanced CT remains a clinical challenge. Therefore, there is a need to evaluate new imaging modalities, such as CT perfusion (CTP) to improve the visualization of coagulation necrosis. MWA and CTP were prospectively performed in five healthy pigs. After the procedure, the pigs were euthanized, and the livers explanted. Orthogonal histological slices of the ablations were stained with a vital stain, digitalized and the necrotic core was segmented. CTP maps were calculated using a dual-input deconvolution algorithm. The segmented necrotic zones were overlaid on the DICOM images to calculate the accuracy of depiction by CECT/CTP compared to the histological reference standard. A receiver operating characteristic analysis was performed to determine the agreement/true positive rate and disagreement/false discovery rate between CECT/CTP and histology. Standard CECT showed a true positive rate of 81% and a false discovery rate of 52% for display of the coagulation necrosis. Using CTP, delineation of the coagulation necrosis could be improved significantly through the display of hepatic blood volume and hepatic arterial blood flow (p < 0.001). The ratios of true positive rate/false discovery rate were 89%/25% and 90%/50% respectively. Other parameter maps showed an inferior performance compared to CECT.

Role of Diffusional Kurtosis Imaging in Evaluating the Efficacy of Transcatheter Arterial Chemoembolization in Patients with Liver Cancer

Objective: To explore the role of diffusional kurtosis imaging (DKI) in evaluating the efficacy of transcatheter arterial chemoembolization (TACE) in patients with liver cancer. Materials and Methods: A total of 54 patients with primary liver cancer underwent TACE were selected as the study subjects. Magnetic resonance imaging and DKI scans were carried out before and after TACE, and the relevant parameters were analyzed. Results: Compared with those before TACE, the values of radial diffusivity (Dr), axial diffusivity (Da), and mean diffusivity (MD) of tumor tissues in the patients after TACE were significantly increased, whereas the values of axial kurtosis (Ka), fractional anisotropy of kurtosis (FAk), hepatic blood volume (HBV), hepatic blood flow (HBF), and hepatic artery perfusion (HAP) were notably decreased (p < 0.05). There were no significant changes regarding FA, radial kurtosis (Kr), mean kurtosis (MK), hepatic arterial fracture (HAF), permeability-surface area product (PS), mean transit time (MTT), and portal vein perfusion (PVP) (p > 0.05). The differences in apparent diffusion coefficients (ADCs) of different liver cancer tissues in patients under different b values after operation were statistically significant, and the ADC values of liver cancer tissues were evidently higher than those of other tumor tissues (p < 0.05). Conclusion: DKI is characterized with advantages such as fastness, simpleness, high resolution, and impregnability of the density of lipiodol. It can not only directly reflect the changes in blood perfusion at the lesion but also accurately and efficiently evaluate the remnants, necrosis, and recurrence of tumor tissues based on changes in ADC under different b values. It provides certain clinical assistance for the evaluation of the efficacy before and after TACE.

Mapping hepatic blood oxygenation by quantitative BOLD (qBOLD) MRI.

Abnormalities in hepatic oxygen delivery and oxygen consumption may serve as a significant indicator of hepatic cellular dysfunction and may predict treatment response. However, conventional and oxygen-enhanced hepatic BOLD MRI can only provide semiquantitative assessment of hepatic oxygenation. A hepatic quantitative BOLD (qBOLD) model was proposed for noninvasive mapping of hepatic venous blood oxygen saturation (Yv ) and deoxygenated blood volume (DBV) in human subjects. The validity and the estimation bias of the proposed model were evaluated by Monte Carlo simulations. Eight healthy subjects were scanned after written consent with institutional review board approval. Monte Carlo simulations demonstrated that the proposed single-compartment hepatic qBOLD model leads to significant deviation of the predicted T2* decay profile from the simulated signal due to high hepatic blood volume fraction. Small relative estimation bias for hepatic Yv and significant overestimation for hepatic DBV were observed, which can be corrected by applying the calibration curves established from simulations. After correction, the mean hepatic Yv in human subjects was 56.8 ± 6.8%, and the mean hepatic DBV was 0.190 ± 0.035, consistent with measurements from other invasive approaches. Except in regions with significant vascular contamination, the maps for hepatic Yv and DBV were relatively homogenous. With estimation bias correction, the hepatic qBOLD approach enables noninvasive mapping of hepatic blood volume and oxygenation in human subjects. The established protocol may be used to quantitatively assess hepatic tissue hypoxia in multiple liver diseases.

Comparison of different 4D CT-Perfusion algorithms to visualize lesions after microwave ablation in an in vivo porcine model

Background: Accurate lesion visualization after microwave ablation (MWA) remains a challenge. Computed tomography perfusion (CTP) has been proposed to improve visualization, but it was shown that different perfusion-models delivered different results on the same data set.Purpose: Comparison of different perfusion algorithms and identification of the algorithm enables for the best imaging of lesion after hepatic MWA.Materials and methods: 10 MWA with consecutive CTP were performed in healthy pigs. Parameter-maps were generated using a single-input-dual-compartment-model with Patlak’s algorithm (PM), a dual-input-maximum-slope-model (DIMS), a dual-input-one-compartment-model (DIOC), a single-(SIDC) and dual-input-deconvolution-model (DIDC). Parameter-maps for hepatic arterial (AF) and portal venous blood flow (PF), mean transit time, hepatic blood volume (HBV) and capillary permeability were compared regarding the values of the normal liver tissue (NLT), lesion, contrast- and signal-to-noise ratios (SNR, CNR) and inter- and intrarater-reliability using the intraclass correlation coefficient, Bland-Altman plots and linear regression.Results: Perfusion values differed between algorithms with especially large fluctuations for the DIOC. A reliable differentiation of lesion margin appears feasible with parameter-maps of PF and HBV for most algorithms, except for the DIOC due to large fluctuations in PF. All algorithms allowed for a demarcation of the central necrotic zone based on hepatic AF and HBV. The DIDC showed the highest CNR and the best inter- and intrarater reliability.Conclusion: The DIDC appears to be the most feasible model to visualize margins and necrosis zones after microwave ablation, but due to high computational demand, a single input deconvolution algorithm might be preferable in clinical practice.

The CCR2+ Macrophage Subset Promotes Pathogenic Angiogenesis for Tumor Vascularization in Fibrotic Livers.

Background & AimsHepatocellular carcinoma (HCC) typically arises in fibrotic or cirrhotic livers, which are characterized by pathogenic angiogenesis. Myeloid immune cells, specifically tumor-associated macrophages (TAMs), may represent potential novel therapeutic targets in HCC, complementing current ablative or immune therapies. However, the detailed functions of TAM subsets in hepatocarcinogenesis have remained obscure.MethodsTAM subsets were analyzed in-depth in human HCC samples and a combined fibrosis–HCC mouse model, established by i.p. injection with diethylnitrosamine after birth and repetitive carbon tetrachloride (CCl4) treatment for 16 weeks. Based on comprehensively phenotyping TAM subsets (fluorescence-activated cell sorter, transcriptomics) in mice, the function of CCR2+ TAM was assessed by a pharmacologic chemokine inhibitor. Angiogenesis was evaluated by contrast-enhanced micro–computed tomography and histology.ResultsWe show that human CCR2+ TAM accumulate at the highly vascularized HCC border and express the inflammatory marker S100A9, whereas CD163+ immune-suppressive TAM accrue in the HCC center. In the fibrosis–cancer mouse model, we identified 3 major hepatic myeloid cell populations with distinct messenger RNA profiles, of which CCR2+ TAM particularly showed activated inflammatory and angiogenic pathways. Inhibiting CCR2+ TAM infiltration using a pharmacologic chemokine CCL2 antagonist in the fibrosis–HCC model significantly reduced pathogenic vascularization and hepatic blood volume, alongside attenuated tumor volume.ConclusionsThe HCC microenvironment in human patients and mice is characterized by functionally distinct macrophage populations, of which the CCR2+ inflammatory TAM subset has pro-angiogenic properties. Understanding the functional differentiation of myeloid cell subsets in chronically inflamed liver may provide novel opportunities for modulating hepatic macrophages to inhibit tumor-promoting pathogenic angiogenesis.

Liver intravoxel incoherent motion diffusion-weighted imaging for the assessment of hepatic steatosis and fibrosis in children.

AIMTo evaluate the correlation between intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) parameters and the degree of hepatic steatosis and fibrosis in children.METHODSThis retrospective study was approved by the institutional review board. The children (≤ 18 years) who underwent liver IVIM DWI with 8 b-values under the suspicion of hepatic steatosis or fibrosis from February 2013 to November 2016 were included. Subjects were divided into normal, fatty liver (FAT), and fibrotic liver (FIB) groups. The slow diffusion coefficient (D), fast diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADC) were measured. MR proton density fat fraction (PDFF), MR elastography (MRE), and IVIM values were compared.RESULTSA total of 123 children (median age of 12 years old, range: 6-18 years) were included, with 8 in the normal group, 93 in the FAT group, and 22 in the FIB group. The D* values were lower in the FIB group compared with those of the normal (P = 0.015) and FAT (P = 0.003) groups. The f values were lower in the FIB group compared with the FAT group (P = 0.001). In multivariate analyses, PDFF value was positively correlated with f value (β = 3.194, P < 0.001), and MRE value was negatively correlated with D* value (β = -7.031, P = 0.032). The D and ADC values were not influenced by PDFF or MRE value.CONCLUSIONIn liver IVIM DWI with multiple b-values in children, there was a positive correlation between hepatic fat and blood volume, and a negative correlation between hepatic stiffness and endovascular blood flow velocity, while diffusion-related parameters were not affected.

Liver blood dynamics after bariatric surgery: the effects of mixed-meal test and incretin infusions.

Aims/hypothesisThe mechanisms for improved glycemic control after bariatric surgery in subjects with type 2 diabetes (T2D) are not fully known. We hypothesized that dynamic hepatic blood responses to a mixed-meal are changed after bariatric surgery in parallel with an improvement in glucose tolerance.MethodsA total of ten morbidly obese subjects with T2D were recruited to receive a mixed-meal and a glucose-dependent insulinotropic polypeptide (GIP) infusion before and early after (within a median of less than three months) bariatric surgery, and hepatic blood flow and volume (HBV) were measured repeatedly with combined positron emission tomography/MRI. Ten lean non-diabetic individuals served as controls.ResultsBariatric surgery leads to a significant decrease in weight, accompanied with an improved β-cell function and glucagon-like peptide 1 (GLP-1) secretion, and a reduction in liver volume. Blood flow in portal vein (PV) was increased by 1.65-fold (P = 0.026) in response to a mixed-meal in subjects after surgery, while HBV decreased in all groups (P < 0.001). When the effect of GIP infusion was tested separately, no change in hepatic arterial and PV flow was observed, but HBV decreased as seen during the mixed-meal test.Conclusions/interpretationEarly after bariatric surgery, PV flow response to a mixed-meal is augmented, improving digestion and nutrient absorption. GIP influences the post-prandial reduction in HBV thereby diverting blood to the extrahepatic sites.

Computed Tomographic Perfusion Imaging for the Prediction of Response and Survival to Transarterial Chemoembolization of Hepatocellular Carcinoma.

BackgroundThe purpose of this retrospective cohort study was to evaluate the clinical value of computed tomographic perfusion imaging (CTPI) parameters in predicting the response to treatment and overall survival in patients with hepatocellular carcinoma (HCC) treated with drug-eluting beads transarterial chemoembolization (DEBTACE).Patients and methodsBetween December 2010 and January 2013 eighteen patients (17 men, 1 woman; mean age 69 ± 5.8 years) with intermediate stage HCC underwent CTPI of the liver prior to treatment with DEBTACE. Treatment response was evaluated on follow-up imaging according to modified Response Evaluation Criteria in Solid Tumors. Pre-treatment CTPI parameters were compared between patients with complete response and partial response with a Student t-test. We compared survival times with Kaplan-Meier method.ResultsCTPI parameters of patients with complete response and others did not show statistical significant difference. The mean survival time was 25.4 ± 3.2 months (95%; CI: 18.7-32.1). Survival was statistically significantly longer in patients with hepatic blood flow (BF) lower than 50.44 ml/100 ml/min (p = 0.033), hepatic blood volume (BV) lower than 13.32 ml/100 ml (p = 0.028) and time to peak (TTP) longer than 19.035 s (p = 0.015).ConclusionsCTPI enables prediction of survival in patients with intermediate stage HCC, treated with DEBTACE based on the pre-treatment values of BF, BV and TTP perfusion parameters. CT perfusion imaging can’t be used to predict treatment response to DEBTACE.

Comparison of microvascular perfusion evaluation among IVIM-DWI, CT perfusion imaging and histological microvessel density in rabbit liver VX2 tumors

ObjectTo explore microcirculation features with intravoxel incoherent motion (IVIM) and to compare IVIM with CT perfusion imaging (CTPI) and microvessel density (MVD). Materials and methodsHepatic CTPI and IVIM were performed in 16 rabbit liver VX2 tumor models. Hepatic arterial perfusion (HAP), hepatic arterial perfusion index (HPI), Blood flow (BF), and blood volume (BV) from CTPI were measured. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) from IVIM were measured. MVD was counted with CD34 stain. The microcirculation features with IVIM were compared with CTPI parameters and MVD. ResultsStrong linear correlations were found between D value (0.89±0.21×10−3mm2/s) and HAP (15.83±6.97ml/min/100mg) (r=0.755, P=0.001) and between f value (12.64±6.66%) and BV (9.74±5.04ml/100mg) (r=0.693, P=0.004). Moderate linear correlations were observed between ADC (1.07±0.32×10−3mm2/s) and HAP (r=0.538, P=0.039), respectively; and between D value and MVD (9.31±2.57 vessels at 400×magnification) (r=0.509, P=0.044). No correlations were found between D* (119.90±37.67×10−3mm2/s) and HAP, HPI (68.34±12.91%), BF (4.95±2.16ml/min/100mg), BV. ConclusionIVIM parameters can characterize microcirculation to certain extent and separate it from pure water molecular diffusion. There is fair correlation between D or ADC value and CTPI parameters or MVD, but no correlation between D* or f value and CTPI parameters or MVD except f value and BV, which is still unclear and need further clinical studies to validate.

Diagnostic value of dynamic contrast-enhanced CT with perfusion imaging in the quantitative assessment of tumor response to sorafenib in patients with advanced hepatocellular carcinoma: A feasibility study

PurposeTo investigate the feasibility of perfusion-CT (p-CT) measurements in quantitative assessment of hemodynamic changes related to sorafenib in patients with advanced hepatocellular carcinoma (HCC). Materials and methodsTwenty-two patients with advanced HCC underwent p-CT study (256-MDCT scanner) before and 2 months after sorafenib administration. Dedicated perfusion software generated a quantitative map of arterial and portal perfusion and calculated the following perfusion parameters in target liver lesion: hepatic perfusion (HP), time-to-peak (TTP), blood volume (BV), arterial perfusion (AP), and hepatic perfusion index (HPI). After the follow-up scan, patients were categorized as responders and non-responders, according to mRECIST. Perfusion values were analyzed and compared in HCC lesions and in the cirrhotic parenchyma (n=22), such as between baseline and follow-up in progressors and non-progressors. ResultsBefore treatment, all mean perfusion values were significantly higher in HCC lesions than in the cirrhotic parenchyma (HP 47.8±17.2 vs 13.3±6.3mL/s per 100g; AP 47.9±18.1 vs 12.9±10.7mL/s; p<0.001). The group that responded to sorafenib (n=17) showed a significant reduction of values in HCC target lesions after therapy (HP 29.2±23.3 vs 48.1±15.1; AP 29.4±24.6 vs 49.2±17.4; p<0.01), in comparison with the non-responder group (n=5) that demonstrated no significant variation before and after treatment of HP (46.9±25.1 vs 46.7±24.1) and AP (43.4±21.7 vs 43.5±24.6). Among the responder group, HP percentage variation (Δ) in target lesions, during treatment, showed a significantly different (p=0.04) ΔHP in the group with complete response (79%) compared to the group with partial response or stable disease (16%). Conclusionsp-CT technique can be used for HCC quantitative assessment of changes related to anti-angiogenic therapy. Identification of response predictors might help clinicians in selection of patients who may benefit from targeted-therapy allowing for optimization of individualized treatment.

Evaluation of efficacy of transcatheter arterial chemoembolization combined with computed tomography-guided radiofrequency ablation for hepatocellular carcinoma using magnetic resonance diffusion weighted imaging and computed tomography perfusion imaging: A prospective study.

Background:The purpose of this study is to evaluate the efficacy of transcatheter arterial chemoembolization (TACE) combined with computed tomography-guided radiofrequency ablation (CT-RFA) in the treatment of hepatocellular carcinoma (HCC) using magnetic resonance diffusion weighted imaging (MR-DWI) and CT perfusion imaging (CT-PI).Methods:From January 2008 to January 2014, a total of 522 HCC patients receiving TACE combined with CT-RFA were included in this study. All patients underwent TACE followed by CT-RFA, and 1 day before treatment and 1 month after treatment they received MR-DWI and CT-PI. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the concentration of alpha-fetoprotein (AFP). Tumor response was evaluated using the revised RECIST criteria. One-year follow-up was conducted on all patients. Receiver-operating characteristic (ROC) curve was drawn to evaluate the efficacy of TACE combined with CT-RFA for HCC using MR-DWI and CT-PI.Results:Total effective rate (complete remission [CR] + partial remission [PR]) of TACE combined with CT-RFA for HCC was 82.95%. HCC patients of CR + PR had lower hepatic blood flow (HBF), hepatic blood volume (HBV), permeability surface (PS), hepatic arterial perfusion (HAP), and hepatic perfusion index (HPI) levels than those of SD + PD, but HCC patients of CR + PR had higher mean transit time (MTT) level than those of SD + PD. The patients of PR + CR had higher apparent diffusion coefficient (ADC) values than those of SD + PD. The patients of PR + CR showed lower AFP concentration than those of SD + PD. ROC curve analysis indicated that the area under the curve (AUC) of AFP, HBV, PS, HAP, HPI, and ADC was more than 0.7, but the AUC of HBF, MTT, and PVP were less than 0.7. After treatment, the AFP, HBF, HBV, PS, HAP, and HPI in the HCC patients with recurrence were higher than those in the HCC patients without, but MTT and ADC in the HCC patients with recurrence were lower than those in the HCC patients without.Conclusion:These findings indicate that MR-DWI and CT-PI can effectively evaluate the efficacy of TACE combined with CT-RFA and postoperative recurrence of HCC.

Detection and differentiation of early hepatocellular carcinoma from cirrhosis using CT perfusion in a rat liver model

Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in hepatocellular carcinoma (HCC). Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investigate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic (ROC) curves. Male Wistar rats were randomly divided into control (n=20) and experimental (n=70) groups. Diethylnitrosamine (DEN) was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion (HPP), hepatic arterial fraction (HAF), hepatic arterial perfusion (HAP), hepatic blood volume (HBV), hepatic blood flow (HBF), mean transit time (MTT) and permeability of capillary vessel surface (PS) data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats (control, pre-carcinoma and early HCC groups) using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan. For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups (P<0.05). HAF had the highest areas under the ROC curves: 0.80 (control vs pre-carcinoma groups) and 0.95 (control vs early HCC groups) with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 (control vs pre-carcinoma groups) and 0.92 (control vs early HCC groups) with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.

Hepatic Blood Volume Imaging with the Use of Flat-Detector CT Perfusion in the Angiography Suite: Comparison with Results of Conventional Multislice CT Perfusion

PurposeTo prospectively determine the feasibility of flat-detector (FD) computed tomography (CT) perfusion to measure hepatic blood volume (BV) in the angiography suite in patients with hepatocellular carcinoma (HCC). Materials and MethodsTwenty patients with HCC were investigated with conventional multislice and FD CT perfusion. CT perfusion was carried out on a multislice CT scanner, and FD CT perfusion was performed on a C-arm angiographic system, before transarterial chemoembolization procedures. BV values of conventional and FD CT perfusion were measured within tumors and liver parenchyma. The arterial perfusion portion of CT perfusion BV was extracted from CT perfusion BV by multiplying it by a hepatic perfusion index. Relative values (RVs) for CT perfusion arterial BV and FD CT perfusion BV (FD BV) were defined by dividing BV of tumor by BV of parenchyma. Relationships between BV and RV values of these two techniques were analyzed. ResultsIn all patients, both perfusion procedures were technically successful, and all 33 HCCs larger than 10 mm were identified with both imaging methods. There were strong correlations between the absolute values of FD BV and CT perfusion arterial BV (tumor, r = 0.903; parenchyma, r = 0.920; both P < .001). Bland–Altman analysis showed a mean difference of −0.15 ± 0.24 between RVs for CT perfusion arterial BV and FD BV. ConclusionsThe feasibility of FD CT perfusion to assess BV values of liver tumor and surrounding parenchyma in the angiographic suite was demonstrated.

Investigation on the optical scan condition for imaging of multi-slice spiral CT liver perfusion in rats

Background Multi-slice CT liver perfusion has been widely used in experimental studies of hemodynamic changes in liver lesions, and is usually performed as an adjunct to a conventional CT examination because of its high temporal and spatial resolution, simple protocol, good reproducibility, and ability to measure hemodynamic changes of liver tissues at the capillary level. Experimental rat models, especially those of induced liver cancer, are often used in studies of hemodynamic changes in liver cancer. Carcinogenesis in rats has a similar pathological progression and characteristics resembling those in human liver cancer; as a result, rat models are often used as ideal animal models in the study of human liver cancer. However, liver perfusion imaging in rats is difficult to perform, because rats' livers are so small that different concentrations, flow rates, and dose of contrast agents during the CT perfusion scanning can influence the quality of liver perfusion images in rats. The purpose of this study, therefore, was to investigate the optimal scan protocol for the imaging of hepatic perfusion using a deconvolution mathematical method in rats by comparing the results of rats in different injection conditions of the contrast agent, including concentration, rate and time. Methods Plain CT scan conditions in eighty 2-month-old male Wistar rats were 5.0 mm slice thickness, 5.0 mm interval, 1.0 pitch, 120 kV tube voltage, 60 mA tube current, 512×512 matrix, and FOV 9.6 cm. Perfusion scanning was carried out with different concentrations of diatrizoate (19%, 38%, 57%, and 76%), different injection rates (0.3 and 0.5 ml/s), and different injection times (1, 2-3, 4-5, and 6 seconds). The above conditions were randomly matched and adjusted to determine the best perfusion scan protocol. Three-phase contrast-enhanced scanning was performed after CT perfusion. Histological examination of the liver tissues with hematoxylin and eosin stains was done after CT scanning. Results When the concentration of the contrast agent was 19% or 38%, no pseudo-color map was created. The viscosity increased when the concentration of the contrast agent was 76%; so it is difficult to inject the contrast agent at such a high concentration. Also no pseudo-color map was generated when the injection time was short (1, 2-3, and 4-5 seconds) or the injection rate was low (0.3 ml/s). The best perfusion images and perfusion parameters were obtained during 50 seconds scanning. Each rat was given an injection of 57% diatrizoate at 0.5 ml/s via the tail vein using a high-pressure syringe for 6 seconds. The perfusion parameters included hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT) of the contrast agent, capillary permeability-surface area product (PS), hepatic arterial index (HAI), hepatic artery perfusion (HAP), and hepatic portal perfusion (HPP). All these parameters reflected the perfusion status of liver parenchyma in normal rats. Three phases of enhancement were modified according to the time-density curves (TDCs) of the perfusion imaging: hepatic arterial phase (7 seconds), hepatic portal venous phase (15 seconds), and a delayed phase (23-31 seconds). On examination by microscopy, the liver tissues were pathologically normal. Conclusions The appropriate protocol with multi-slice spiral CT liver perfusion reflected normal liver hemodynamics in rats. This study laid a solid foundation for further investigation of the physiological characteristics of liver cancer in a rat model, and was an important supplement to and reference for conventional contrast-enhanced CT scans.

CT assessment of liver hemodynamics in patients with hepatocellular carcinoma after argon-helium cryoablation

Assessment of tumor response after argon-helium cryoablation is critical in guiding future therapy for unresectable hepatocellular carcinoma. This study aimed to evaluate liver hemodynamics in hepatocellular carcinoma after argon-helium cryoablation with computed tomography perfusion. The control group comprised 40 volunteers without liver disease. The experimental group was composed of 15 patients with hepatocellular carcinoma treated with argon-helium cryoablation. Computed tomography perfusion parameters were measured: hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. After treatment, in the tumor foci, permeability of capillary vessel surface was higher, and hepatic blood flow, hepatic blood volume, hepatic arterial fraction, and hepatic arterial perfusion values were lower (P<0.05). In the liver parenchyma surrounding the tumor, hepatic arterial perfusion was significantly lower (P<0.05); however, there was no significant difference in hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial fraction, or hepatic portal perfusion (P>0.05). Computed tomography perfusion can evaluate tumor response after argon-helium cryoablation.

Hemodynamic study of hepatocellular carcinoma nodules by multi-slice spiral computed tomographic perfusion

To analyze the 64-slice computed tomographic (CT) perfusion parameters of hepatocellular carcinoma (HCC) nodule so as to assess the diagnostic value of hemodynamic changes of HCC nodule by this perfusion technique. Forty volunteers without liver disease (control subjects) and 37 HCC patients (experimental group) were selected. After informed consents, all of them underwent plain, perfusion and contrast CT examinations. Perfusion CT scan was performed at 120 kV, 60 mA and a thickness of up to 40 mm. The injection rate of contrast medium was 4 - 5 ml/sec at a dose of 1.0 ml/kg body weight. And 50 seconds of continuous scanning time was set at 5 seconds post-injection. The indices were 1 second per 360° revolution, 5 mm slice thickness image reconstruction and a matrix size of 512×512 pixels. Perfusion parameters associated with changes in hepatic blood flow included blood flow (HBF), hepatic blood volume (HBV), hepatic arterial perfusion index (HAI), hepatic artery perfusion (HAP) and portal venous perfusion (HPP). Perfusion parameters were measured thrice at each time point for each different region of interest (ROI): hepatic parenchyma surrounding HCC nodule, HCC nodule and normal liver parenchyma(control group). For HCC nodule, the increased levels of HBF, HAP and HAI were significantly differentiated from normal liver parenchyma of control group (P < 0.01). Increased HBV and decreased HPP had no difference from control group (P > 0.05). Higher levels of HAP, HPP and HAI in HCC nodules were differentiated from hepatic parenchyma surrounding HCC nodules (P < 0.05). HBV decreased and HBF increased in HCC nodule. But it had no differences from hepatic parenchyma surrounding HCC nodule (P > 0.05). Perfusion CT may visualize the status of liver blood flow caused by HCC nodule so as to serve as a new tool of studying the hemodynamic changes of HCC nodules.

Evaluating the effect of high-intensity focused ultrasound therapy on liver tumors using multislice CT perfusion

The aim of this study was to investigate the changes of the multislice computed tomography (MSCT) perfusion parameters and histopathology of the liver in rabbits with VX2 tumors before and after high-intensity focused ultrasound (HIFU) therapy. VX2 carcinoma cells were implanted into the livers of eight New Zealand white rabbits 3 weeks prior to the treatment. MSCT perfusion was performed one week before and one and six weeks after the treatment. These CT perfusion (CTP) data, including hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT) and permeability-surface area product (PS), were analyzed semi-quantitatively and qualitatively. Furthermore, the histopathological features of the liver tissues were also assessed semi-quantitatively before and after the treatment. Six weeks after HIFU therapy, MTT increased noticeably from 5.45±0.27 to 10.38±2.22 sec (P<0.05) and PS decreased significantly from 79.03±3.41 to 68.13±0.21 ml/100 g/min (P<0.05), while no significant differences in HBF and HBV were found. Furthermore, more CD3+ T cells were observed at the rim and center of the liver tumors six weeks after treatment. Therefore, HIFU therapy may be a simple and effective method for the treatment of liver tumors. CTP, as an effective method to obtain functional information about HBF, is able to quantify tumor vascularity and angiogenesis in liver tumors.

Early changes of hepatic hemodynamics measured by functional CT perfusion in a rabbit model of liver tumor

Early detection and treatment of hepatocellular carcinoma is crucial to improving the patients' survival. The hemodynamic changes caused by tumors can be serially measured using CT perfusion. In this study, we used a CT perfusion technique to demonstrate the changes of hepatic hemodynamics in early tumor growth, as a proof-of-concept study for human early hepatocellular carcinoma. VX2 tumors were implanted in the liver of ten New Zealand rabbits. CT perfusion scans were made 1 week (early) and 2 weeks (late) after tumor implantation. Ten normal rabbits served as controls. CT perfusion parameters were obtained at the tumor rim, normal tissue surrounding the tumor, and control liver; the parameters were hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial index, hepatic arterial perfusion and hepatic portal perfusion. Microvessel density and vascular endothelial growth factor were correlated. At the tumor rim, compared to the controls, hepatic blood flow, hepatic blood volume, permeability of capillary vessel surface, hepatic arterial index, and hepatic arterial perfusion increased, while mean transit time and hepatic portal perfusion decreased on both early and late scans (P<0.05). Hepatic arterial index increased (135%, P<0.05), combined with a sharp increase in hepatic arterial perfusion (182%, P<0.05) and a marked decrease in hepatic portal perfusion (-76%, P<0.05) at 2 weeks rather than at 1 week (P<0.05). Microvessel density and vascular endothelial growth factor showed significant linear correlations with hepatic blood flow, permeability of capillary vessel surface and hepatic arterial index, but not with hepatic blood volume or mean transit time. The CT perfusion technique demonstrated early changes of hepatic hemodynamics in this tumor model as proof-of-concept for early hepatocellular carcinoma detection in humans.