Discrimination between patients with mild Alzheimer's disease and healthy subjects based on cerebral blood flow images of the lateral views in xenon-enhanced computed tomography.

BACKGROUND: Quantitative cerebral blood flow (CBF) measurement is expected to help early detection of functional abnormalities caused by Alzheimer's disease (AD) and enable AD treatment to begin in its early stages. Recently, a technique of layer analysis was reported that allowed CBF to be analyzed from the outer to inner layers of the brain. The aim of this work was to develop methods for discriminating between patients with mild AD and healthy subjects based on CBF images of the lateral views created with the layer analysis technique in xenon-enhanced computed tomography. METHODS: Xenon-enhanced computed tomography using a wide-volume CT was performed on 17 patients with mild AD aged 75 or older and on 15 healthy age-matched volunteers. For each subject, we created CBF images of the right and left lateral views with a depth of 10-15 mm from the surface of the brain. Ten circular regions of interest (ROI) were placed on each image, and CBF was calculated for each ROI. We determined discriminant ROI that had CBF that could be used to differentiate between the AD and volunteer groups. AD patients' CBF range (mean - SD to mean + SD) and healthy volunteers' CBF range (mean - SD to mean + SD) were obtained for each ROI. Receiver-operator curves were created to identify patients with AD for each of the discriminant ROI and for the AD patients' and healthy volunteers' CBF ranges. RESULTS: We selected an ROI on both the right and left temporal lobes as the discriminant ROI. Areas under the receiver-operator curve were 93.3% using the ROI on the right temporal lobe, 95.3% using the ROI on the left temporal lobe, and 92.4% using the AD patients' and healthy volunteers' CBF ranges. CONCLUSIONS: We could effectively discriminate between patients with mild AD and healthy subjects using ROI placed on CBF images of the lateral views in xenon-enhanced computed tomography.

Consideration of the Intracranial Pressure Threshold Value for the Initiation of Traumatic Brain Injury Treatment: A Xenon CT and Perfusion CT Study.

BACKGROUND: Monitoring of intracranial pressure (ICP) is considered to be fundamental for the care of patients with severe traumatic brain injury (TBI) and is routinely used to direct medical and surgical therapy. Accordingly, some guidelines for the management of severe TBI recommend that treatment be initiated for ICP values >20 mmHg. However, it remained to be accounted whether there is a scientific basis to this instruction. The purpose of the present study was to clarify whether the basis of ICP values >20 mmHg is appropriate. SUBJECT AND METHODS: We retrospectively reviewed 25 patients with severe TBI who underwent neuroimaging during ICP monitoring within the first 7 days. We measured cerebral blood flow (CBF), mean transit time (MTT), cerebral blood volume (CBV), and ICP 71 times within the first 7 days. RESULTS: Although the CBF, MTT, and CBV values were not correlated with the ICP value at ICP values ≤20 mmHg, the CBF value was significantly negatively correlated with the ICP value (r = -0.381, P < 0.05) at ICP values >20 mmHg. The MTT value was also significantly positively correlated with the ICP value (r = 0.638, P < 0.05) at ICP values >20 mmHg. CONCLUSION: The cerebral circulation disturbance increased with the ICP value. We demonstrated the cerebral circulation disturbance at ICP values >20 mmHg. This study suggests that an ICP >20 mmHg is the threshold to initiate treatments. An active treatment intervention would be required for severe TBI when the ICP was >20 mmHg.

Discrimination Between Patients With Alzheimer Disease and Healthy Subjects Using Layer Analysis of Cerebral Blood Flow and Xenon Solubility Coefficient in Xenon-Enhanced Computed Tomography.

OBJECTIVE: The aim of this study was to develop a method for discriminating between patients with Alzheimer disease (AD) and healthy subjects using layer analysis of cerebral blood flow (CBF) and xenon solubility coefficient (λ) in xenon-enhanced computed tomography (CT). METHODS: Xenon-enhanced CT was performed on 27 patients with AD (81.7 [3.3] years old) and 15 healthy volunteers (78.6 [4.0] years old) using a wide volume CT. For each subject, we created the first- (surface) to sixth-layer images of CBF and λ for the 6 viewing directions (layer thickness, 5 mm). For the discriminant views, receiver operating characteristic curves for the ratio of CBF to λ were created to identify patients with AD. RESULTS: For the third- and fourth-layer left lateral views, which were designated as the discriminant views, areas under the receiver operating characteristic curve were 96.8% and 97.4%, respectively. CONCLUSIONS: With the use of the discriminant views obtained by xenon-enhanced CT, we could effectively discriminate between patients with AD and healthy subjects using both CBF and λ.

Correlations of Hepatic Hemodynamics, Liver Function, and Fibrosis Markers in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis Related to Hepatitis C Virus.

The progression of chronic liver disease differs by etiology. The aim of this study was to elucidate the difference in disease progression between chronic hepatitis C (CHC) and nonalcoholic fatty liver disease (NAFLD) by means of fibrosis markers, liver function, and hepatic tissue blood flow (TBF). Xenon computed tomography (Xe-CT) was performed in 139 patients with NAFLD and 152 patients with CHC (including liver cirrhosis (LC)). The cutoff values for fibrosis markers were compared between NAFLD and CHC, and correlations between hepatic TBF and liver function tests were examined at each fibrosis stage. The cutoff values for detection of the advanced fibrosis stage were lower in NAFLD than in CHC. Although portal venous TBF (PVTBF) correlated with liver function tests, PVTBF in initial LC caused by nonalcoholic steatohepatitis (NASH-LC) was significantly lower than that in hepatitis C virus (C-LC) (p = 0.014). Conversely, the liver function tests in NASH-LC were higher than those in C-LC (p < 0.05). It is important to recognize the difference between NAFLD and CHC. We concluded that changes in hepatic blood flow occurred during the earliest stage of hepatic fibrosis in patients with NAFLD; therefore, patients with NAFLD need to be followed carefully.

Correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis.

AIM: To elucidate the correlation between hepatic blood flow and liver function in alcoholic liver cirrhosis (AL-LC). METHODS: The subjects included 35 patients with AL-LC (34 men, 1 woman; mean age, 58.9 ± 10.7 years; median age, 61 years; range: 37-76 years). All patients were enrolled in this study after obtaining written informed consent. Liver function was measured with tests measuring albumin (Alb), prothrombin time (PT), brain natriuretic peptide (BNP), branched amino acid and tyrosine ratio (BTR), branched chain amino acid (BCAA), tyrosine, ammonia (NH3), cholinesterase (ChE), immunoreactive insulin (IRI), total bile acid (TBA), and the retention rate of indocyanine green 15 min after administration (ICG R15). Hepatic blood flow, hepatic arterial tissue blood flow (HATBF), portal venous tissue blood flow (PVTBF), and total hepatic tissue blood flow (THTBF) were simultaneously calculated using xenon computed tomography. RESULTS: PVTBF, HATBF and THTBF were 30.2 ± 10.4, 20.0 ± 10.7, and 50.3 ± 14.9 mL/100 mL/min, respectively. Alb, PT, BNP, BTR, BCAA, tyrosine, NH3, ChE, IRI, TBA, and ICG R15 were 3.50 ± 0.50 g/dL, 72.0% ± 11.5%, 63.2 ± 56.7 pg/mL, 4.06 ± 1.24, 437.5 ± 89.4 µmol/L, 117.7 ± 32.8 µmol/L, 59.4 ± 22.7 µg/dL, 161.0 ± 70.8 IU/L, 12.8 ± 5.0 µg/dL, 68.0 ± 51.8 µmol/L, and 28.6% ± 13.5%, respectively. PVTBF showed a significant negative correlation with ICG R15 (r = -0.468, P <0.01). No significant correlation was seen between ICG 15R, HATBF and THTBF. There was a significant correlation between PVTBF and Alb (r = 0.2499, P < 0.05), and NH3 tended to have an inverse correlation with PVTBF (r = -0.2428, P = 0.0894). There were also many significant correlations between ICG R15 and liver function parameters, including Alb, NH3, PT, BNP, TBA, BCAA, and tyrosine (r = -0.2156, P < 0.05; r = 0.4318, P < 0.01; r = 0.4140, P < 0.01; r = 0.3610, P < 0.05; r = 0.5085, P < 0.001; r = 0.4496, P < 0.01; and r = 0.4740, P < 0.05, respectively). CONCLUSION: Our investigation showed that there is a close correlation between liver function and hepatic blood flow.

Evaluation of hepatic tissue blood flow using xenon computed tomography with fibrosis progression in nonalcoholic fatty liver disease: comparison with chronic hepatitis C.

AIMS: The present study evaluated the utility of xenon computed tomography (Xe-CT) as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF) in patients with nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C (CH-C). METHODS: Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined. RESULTS: In group 1, portal venous TBF (PVTBF), hepatic arterial (HATBF), and total hepatic TBF (THTBF) were significantly lower in patients with in nonalcoholic steatohepatitis (NASH) than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively). In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively). In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C. CONCLUSIONS: PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.

Early cerebral circulation disturbance in patients suffering from different types of severe traumatic brain injury: a xenon CT and perfusion CT study.

INTRODUCTION: Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). In particular, secondary brain insults have been reported to decrease CBF. The purpose of this study was to clarify the cerebral circulation in different types of TBI. METHODS: Sixty-nine patients with TBI were divided into four groups, the subdural hematoma group, the contusion/intracerebral hematoma group, the diffuse axonal injury group, and the diffuse brain swelling group. In these patients, we simultaneously performed Xe-CT and perfusion CT to evaluate the cerebral circulation on post-injury days 1-3. We measured CBF using Xe-CT and mean transit time using perfusion CT and calculated the cerebral blood volume using the AZ-7000 W98 computer system. RESULTS: There were no significant differences in the Glasgow Coma Scale score on arrival or the Glasgow Outcome Scale score between the groups. The patients who had suffered focal TBI displayed more significant cerebral circulation disturbances than those that had suffered diffuse TBI. We were able to evaluate the cerebral circulation of TBI patients using these parameters. CONCLUSION: Moderate hypothermia therapy, which decreases CBF, the cerebral metabolic rate oxygen consumption (CMRO2), and intracranial pressure might be effective against the types of TBI accompanied by cerebral circulation disturbance. We have to use all possible measures including hypothermia therapy to treat severe TBI patients according to the type of TBI that they have suffered.

Xenon computed tomography can evaluate the improvement of hepatic hemodynamics before and after endoscopic injection sclerotherapy.

BACKGROUND: Xenon computed tomography (Xe-CT) provides quantitative information on tissue blood flow (TBF). In the present study, Xe-CT was performed in patients with esophagogastric varices (EGV) before and after endoscopic injection sclerotherapy (EIS) to evaluate hepatic blood flow (HBF), hepatic arterial TBF (HATBF) and portal venous TBF (PVTBF). METHODS: Subjects comprised of 88 patients with EGV (49 men, 39 women, average age 65.8 ± 11.5 years, median age 68 years, 30-86 years) and liver cirrhosis related to either hepatitis C virus (C) (n = 33), hepatitis B virus (B) (n = 3), alcohol (AL) (n = 22), AL + C (n = 7), AL + B (n = 1), B + C + AL (n = 1), nonalcoholic steatohepatitis (NASH) (n = 4), autoimmune hepatitis (AIH) (n = 5), primary biliary cirrhosis (PBC) (n = 2), or cryptogenic (n = 10) were enrolled. All patients, who were enrolled in this study, were performed EIS for prophylaxis. Xe-CT and measurement of the retention rate of indocyanine green 15 min after administration (ICG R15) were performed before and after EIS. Total hepatic TBF (THTBF) and PVTBF/HATBF ratio (P/A) were also calculated. RESULTS: PVTBF, HATBF, THTBF, P/A and ICG R15 before EIS were 28.3 ± 8.91, 22.5 ± 14.4 and 50.8 ± 17.6 ml/100 ml/min, 1.62 ± 0.71 and 28.8 ± 12.7 %, respectively and those after EIS were 31.9 ± 10.0, 19.3 ± 11.6, and 51.2 ± 17.0 ml/100 ml/min, 1.92 ± 0.84 and 23.6 ± 11.3 %, respectively. PVTBF and P/A after EIS were significantly higher than those before EIS (p = 0.00444, p = 0.0179, respectively), and HATBF and ICG R15 after EIS were significantly lower than those before EIS (p = 0.00129, p < 0.001, respectively). CONCLUSIONS: Xenon computed tomography showed that PVTBF increased after EIS for EGV and HATBF decreased in response to an increase in PVTBF.

Measurement of blood flow and xenon solubility coefficient in the human liver by xenon-enhanced computed tomography.

PURPOSE: The goal of this work was to develop a method of calculating blood flow and xenon solubility coefficient (λ) in the hepatic tissue by xenon-enhanced computed tomography (Xe-CT) and to demonstrate λ can be used as a measure of fat content in the human liver. METHODS: A new blood supply model is introduced which incorporates both arterial blood and portal venous blood which join and together flow into hepatic tissue. We applied Fick's law to the model. It was theoretically derived that the time course of xenon concentration in the inflow blood (the mixture of the arterial blood and the portal venous blood) can be approximated by a monoexponential function. This approximation made it possible to obtain the time-course change rate (K(I)) of xenon concentration in the inflow blood using the time course of xenon concentration in the hepatic tissue by applying the algorithm we had reported previously. K(I) was used to calculate blood flow and λ for each pixel in the CT image of the liver. Twenty-six patients (49.2 ± 18.3 years) with nonalcoholic steatohepatitis underwent Xe-CT abdominal studies and liver biopsies. Steatosis of the liver was evaluated using the biopsy specimen and its severity was divided into ten grades according to the fat deposition percentage [(severity 1) ≤ 10%, 10 % <(severity 2) ≤ 20%, [ellipsis (horizontal)], 90% < (severity 10) ≤ 100%]. For each patient, blood flow and λ maps of the liver were created, and the average λ value (λ) was compared with steatosis severity and with the CT value ratio of the liver to the spleen (liver∕spleen ratio). RESULTS: There were good correlations between λ and steatosis severity (r = 0.914, P < 0.0001), and between λ and liver∕spleen ratio (r = -0.881, P < 0.0001). Ostwald solubility for xenon in the hepatic tissue (tissue Xe solubility), which is calculated using λ and the hematocrit value of the patient, also showed a good correlation with steatosis severity (r = 0.910, P < 0.0001). λ ranged from 0.86 to 7.81, and tissue Xe solubility ranged from 0.12 to 1.16. This range of solubility is reasonable considering the reported Ostwald solubility coefficients for xenon in the normal liver and in the fat tissue are 0.10 and 1.3, respectively, at 37 °C. The average blood flow value ranged from 15.3 to 53.5 ml∕100 ml tissue∕min. CONCLUSIONS: A method of calculating blood flow and λ in the hepatic tissue was developed by means of Xe-CT. This method would be valid even if portosystemic shunts exist; it is shown that λ maps can be used to deduce fat content in the liver. As a noninvasive modality, Xe-CT would be applicable to the quantitative study of fatty change in the human liver.

The study of systemic general circulation disturbance during the initiation of therapeutic hypothermia: Pit fall of hypothermia.

AIMS: Neurointensive care has reduced the mortality and improved the outcome of patients for severe brain damage, over recent decades, and made it possible to perform this therapy in safety. However, we have to understand the complications of this therapy well. The purpose of our study was to determine the systemic circulation disturbance during the initiation of therapeutic hypothermia by using this continuous neurointensive monitoring system. MATERIALS AND METHODS: Ten severe brain damage patients treated with hypothermia were enrolled. All patients had Glasgow Coma Scale (GCS) less than or equal to 8, on admission. RESULTS: We verified that heart rate, cardiac output, and oxygen delivery index (DO2I) decreased with decreasing core temperature. We recognized that depressed cardiac index (CI) was attributed to bradycardia, dehydration, and increased systemic vascular resistance index (SVRI) upon initiation of hypothermia. CONCLUSION: Although the hypothermia has a therapeutic role in severe brain damage patients, we have to carry out this therapy while maintaining their cardiac output using multimodality monitoring devices during hypothermia period.

Early cerebral circulatory disturbance in patients suffering subarachnoid hemorrhage prior to the delayed cerebral vasospasm stage: xenon computed tomography and perfusion computed tomography study.

Subarachnoid hemorrhage (SAH) causes dynamic changes in cerebral blood flow (CBF), and results in delayed ischemia due to vasospasm, and early perfusion deficits before delayed cerebral vasospasm (CVS). The present study examined the severity of cerebral circulatory disturbance during the early phase before delayed CVS and whether it can be used to predict patient outcome. A total of 94 patients with SAH underwent simultaneous xenon computed tomography (CT) and perfusion CT to evaluate cerebral circulation on Days 1-3. Cerebral blood flow (CBF) was measured using xenon CT and the mean transit time (MTT) using perfusion CT and calculated cerebral blood volume (CBV). Outcome was evaluated with the Glasgow Outcome Scale (good recovery [GR], moderate disability [MD], severe disability [SD], vegetative state [VS], or death [D]). Hunt and Hess (HH) grade II patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. HH grade III patients displayed significantly higher CBF and lower MTT than HH grade IV and V patients. Patients with favorable outcome (GR or MD) had significantly higher CBF and lower MTT than those with unfavorable outcome (SD, VS, or D). Discriminant analysis of these parameters could predict patient outcome with a probability of 74.5%. Higher HH grade on admission was associated with decreased CBF and CBV and prolonged MTT. CBF reduction and MTT prolongation before the onset of delayed CVS might influence the clinical outcome of SAH. These parameters are helpful for evaluating the severity of SAH and predicting the outcomes of SAH patients.

Pathophysiological analysis of nonalcoholic fatty liver disease by evaluation of fatty liver changes and blood flow using xenon computed tomography: can early-stage nonalcoholic steatohepatitis be distinguished from simple steatosis?

INTRODUCTION: Effective noninvasive tests that can distinguish early-stage nonalcoholic steatohepatitis (NASH) from simple steatosis (SS) have long been sought. Our aim was to determine the possibility of noninvasively distinguishing early-stage NASH from SS. MATERIALS AND METHODS: We used Fick's principle and the Kety-Schmidt equation to determine the hepatic tissue blood flow (TBF) in 65 NASH patients who underwent xenon computed tomography (Xe-CT). We calculated the lambda value (LV), i.e., Xe gas solubility coefficient, in liver and blood. We assessed the histological severity of fatty changes and fibrosis on the basis of Brunt's classification. Liver biopsy revealed SS in 9 patients and NASH in 56 patients. NASH stages 1 and 2 were classified as early-stage NASH (Ea-NASH; 38 patients) and stages 3 and 4 as advanced-stage NASH (Ad-NASH; 18 patients). We evaluated the differences in LV and TBF among the 3 groups. RESULTS: LV was significantly lower in the Ad-NASH group than in the SS and Ea-NASH groups. Portal venous TBF (PVTBF) was significantly lower in the Ea-NASH group than in the SS group, and PVTBF was lower in the Ad-NASH group than in the Ea-NASH group. Total hepatic TBF (THTBF) was significantly different between the SS and Ea-NASH groups and between the SS and Ad-NASH groups. CONCLUSIONS: In conclusion, measurements of TBF and LV are useful for evaluating the pathophysiological progression of NASH. In addition, these measurements can facilitate the differential diagnosis of SS and Ea-NASH, which may not be distinguishable by other means.

Subtraction lung image for evaluating pulmonary ventilation in xenon-enhanced CT.

PURPOSE: The goal of this work was to develop a method of transforming a xenon-enhanced CT (Xe-CT) image of the lung, so as to overlap well with its baseline CT image, and creating a subtraction image (enhanced image minus baseline image), and to demonstrate the possibility of evaluating pulmonary ventilation using the subtraction image. METHODS: Eight healthy men (37.1 +/- 10.1 yr) underwent Xe-CT lung studies. In protocol 1 for five subjects, 30% nonradioactive xenon (Xe) was inhaled for 2 min (washin) followed by air breathing for 4 min (washout). In protocol 2 for three subjects, only washin (30% Xe) for 2 min was applied. In each study, a specific range of the thorax (30 mm) in the supine position was scanned cranio-caudally three times in the helical mode: At the start and end of washin and at the end of washout in protocol 1 and at 1 min intervals from the start to end of washin in protocol 2. After each study, 10-mm-thick CT images were reconstructed to have similar anatomical structures throughout the study. Two-dimensional geometrical warping was performed on enhanced CT images so that they could geometrically overlap with the baseline CT image. Second to eighth degree polynomials were applied to the warping functions. RESULTS: It was derived from the Kety model that subtraction images during washin would directly reflect pulmonary ventilation. Geometrical warping achieved an increase of 0.3%-22.0% in the area, for which ventilation could be evaluated in the subtraction image. In the cases in protocol 2 where the initial lung volume was well retained throughout the study, the ratios of the specific ventilation from the subtraction image to that from the specific ventilation map were 0.88 +/- 0.06 and 0.96 +/- 0.10 for the right and left lungs, respectively. CONCLUSIONS: A subtraction lung image during washin would provide quantitative information on pulmonary ventilation when the baseline and enhanced images could have close lung volume and these two images could overlap well. Image subtraction requires only two scans and therefore less radiation exposure compared to ordinary protocols in Xe-CT. The proposed Xe-CT subtraction method with the geometrical warping technique could be clinically utilized for evaluating pulmonary ventilation.

Evaluation of quantitative portal venous, hepatic arterial, and total hepatic tissue blood flow using xenon CT in alcoholic liver cirrhosis-comparison with liver cirrhosis related to hepatitis C virus and nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Xenon computed tomography (Xe-CT) is a noninvasive method of quantifying and visualizing tissue blood flow (TBF). For the liver, Xe-CT allows separate measurement of hepatic arterial and portal venous TBF. The present study evaluated the usefulness of Xe-CT as a noninvasive diagnostic procedure for measuring hepatic TBF in alcoholic liver cirrhosis (AL-LC), compared with liver cirrhosis related to nonalcoholic steatohepatitis (NASH), (NASH-LC), and hepatitis C virus (HCV), (C-LC). METHODS: Xe-CT was performed on 22 patients with AL-LC, 7 patients with NASH-LC, and 24 patients with C-LC. Severity of LC was classified according to Child-Pugh classification. Correlations between hepatic TBF, Child-Pugh classification, and indocyanin green retention (ICG) rate after 15 minutes (ICG15R) were examined. Correlations of hepatic TBF in Child-Pugh class A to AL-LC, NASH-LC, and C-LC were also examined. RESULTS: Portal venous TBF (PVTBF) displayed a significant negative correlation with Child-Pugh score and ICG15R (r = -0.432, p < 0.01, r = -0.442, p < 0.01, respectively). Moreover, ICG15R displayed a significant positive correlation with Child-Pugh score (r = 0.661, p < 0.001). Meanwhile, mean PVTBF and total hepatic TBF (THTBF) was significantly lower in AL-LC than in C-LC (p < 0.05). Mean PVTBF was significantly lower in Child-Pugh class A to AL-LC and NASH-LC than in that to C-LC (p < 0.05). Similarly, mean THTBF was significantly lower in Child-Pugh class A to NASH-LC than in that to C-LC (p < 0.05). CONCLUSIONS: Measurement of hepatic TBF using Xe-CT is useful as a noninvasive, objective method of assessing the state of the liver in chronic liver disease.

Assessment of hepatic steatosis and hepatic tissue blood flow by xenon computed tomography in nonalcoholic steatohepatitis.

AIM: The diagnosis of non-alcoholic steatohepatitis (NASH) can be difficult using blood tests and imaging studies. Histological diagnosis by liver biopsy remains the gold standard of NASH diagnosis. There is an urgent need to develop and validate simple, reproducible, noninvasive tests to accurately assess NASH stage and grade. We assess the usefulness of xenon computed tomography (Xe-CT), as a non-invasive method of quantitatively and visually determining hepatic tissue blood flows (TBFs), and xenon solubility (lambda value) simultaneously with TBF, in the evaluation of NASH pathophysiology. METHODS: Histological severity of fatty changes and severity of fibrosis based on Brunt's classification were determined in 38 NASH patients. We evaluated correlations between the grade of fatty changes and lambda value, and correlations between the stage of fibrosis and TBFs. RESULTS: The lambda value showed significant positive correlations with both grade of steatosis (r = 0.813, P < 0.001) and each 10% range of histological fatty infiltration (r = 0.926, P < 0.001). A significant negative correlation was seen between lambda value and the liver : spleen ratio (r = -0.835, P < 0.001). Portal venous tissue blood flow and total hepatic tissue blood flow showed significant negative correlations with the progression of fibrosis (r = -0.465, P < 0.01; r = -0.433, P < 0.01, respectively). Total hepatic tissue blood flow tended to decrease with progressing grade of steatosis. CONCLUSION: Xe-CT offers a convenient and objective method for evaluating fatty infiltration and changes in blood flow in the entire liver, and appears useful for detailed evaluation of patients with NASH.

Determination of time-course change rate for arterial xenon using the time course of tissue xenon concentration in xenon-enhanced computed tomography.

In calculating tissue blood flow (TBF) according to the Fick principle, time-course information on arterial tracer concentration is indispensable and has a considerable influence on the accuracy of calculated TBF. In TBF measurement by xenon-enhanced computed tomography (Xe-CT), nonradioactive xenon gas is administered by inhalation as a tracer, and end-tidal xenon is used as a substitute for arterial xenon. There has been the assumption that the time-course change rate for end-tidal xenon concentration (Ke) and that for arterial xenon concentration (Ka) are substantially equal. Respiratory gas sampling is noninvasive to the patient and Ke can be easily measured by exponential curve fitting to end-tidal xenon concentrations. However, it is pointed out that there would be a large difference between Ke and Ka in many cases. The purpose of this work was to develop a method of determining the Ka value using the time course of tissue xenon concentration in Xe-CT. The authors incorporated Ka into the Kety autoradiographic equation as a parameter to be solved, and developed a method of least-squares to obtain the solution for Ka from the time-course changes in xenon concentration in the tissue. The authors applied this method of least-squares to the data from Xe-CT abdominal studies performed on 17 patients; the solution for Ka was found pixel by pixel in the spleen, and its Ka map was created for each patient. On the one hand, the authors obtained the average value of the Ka map of the spleen as the calculated Ka (Ka(calc)) for each patient. On the other hand, the authors measured Ka (Ka(meas)) using the time-course changes in CT enhancement in the abdominal aorta for each patient. There was a good correlation between Ka(calc), and Ka(meas) (r = 0.966, P < 0.0001), and these two Ka values were close to each other (Ka(calc) = 0.935 x Ka(meas) + 0.089). This demonstrates that K(cala) would be close to the true Ka value. Accuracy of TBF by Xe-CT can be improved with use of the average value of the Ka map of an organ like the spleen that has a single blood supply (only arterial inflow).

Evaluation of quantitative portal venous, hepatic arterial, and total hepatic tissue blood flow using xenon CT in alcoholic liver cirrhosis: comparison with liver cirrhosis C.

BACKGROUND/AIMS: Xenon computed tomography (Xe-CT) is a noninvasive method of quantifying and visualizing tissue blood flow (TBF). For the liver, Xe-CT allows separate measurement of hepatic arterial and portal venous TBF. The present study evaluated the usefulness of Xe-CT as a noninvasive diagnostic procedure for measuring hepatic TBF in alcoholic liver cirrhosis (AL-LC), compared with liver cirrhosis C (C-LC). METHODS: Xenon computed tomography was performed on 12 patients with AL-LC and 17 patients with C-LC. The severity of LC was classified according to Child-Pugh classification. Correlations between hepatic TBF and Child-Pugh classification were examined. Correlations of hepatic TBF in Child-Pugh class A to C-LC and AL-LC were also examined. RESULTS: The mean portal venous TBF (PVTBF) was significantly lower in AL-LC than in C-LC (p=0.0316). Similarly, the mean total hepatic TBF (THTBF) was significantly lower in AL-LC than in C-LC (p=0.0390). PVTBF displayed a significant negative correlation with Child-Pugh score (r=-0.396, p=0.0368). CONCLUSIONS: Measurement of hepatic TBF using Xe-CT is useful as a noninvasive, objective method of assessing the state of the liver in chronic liver disease.

Xenon computed tomography shows hemodynamic change during the progression of chronic hepatitis C.

AIM: Xenon computed tomography (Xe-CT) is a non-invasive method of quantifying and visualizing tissue blood flow (TBF). Xe-CT allows separate measurement of hepatic arterial and portal venous flow. The aim of this study was to investigate correlations between the progression of fibrosis and hemodynamic changes in chronic hepatitis C (CHC) patients using Xe-CT. METHODS: Separate measurements of portal venous TBF (PVTBF) and hepatic arterial TBF (HATBF) were performed using Xe-CT, and total hepatic TBF (THTBF) was calculated as the sum of PVTBF and HATBF. A total of 50 patients with CHC underwent Xe-CT. Liver biopsy was performed on 42 of the 50 patients, and hepatic fibrosis was classified as mild (F1), moderate (F2), severe (F3) or Child-Pugh class A cirrhosis (F4a). In addition, eight patients with Child-Pugh class B cirrhosis (F4b) were evaluated. RESULTS: Significant negative correlations were identified between PVTBF and progression of stage (r(s) = -0.622, P < 0.0001) and between THTBF and progression of stage (r(s) = -0.458, P = 0.0041). CONCLUSION: Separate measurement of PVTBF and HATBF using non-invasive Xe-CT provided quantitative and visual information regarding hemodynamics of the entire liver in CHC patients. PVTBF decreases with the progression of fibrosis, even in CHC patients.

Determination of gate-on and -off timing in respiration-gated radiotherapy.

The purpose of this study was to develop an efficient method of determining gate-on and -off timing in respiration-gated radiotherapy. Gate-on and -off timing in a breathing cycle were defined as the respiratory signal level for the start of irradiation (Ls) in the expiration phase and that for the end of irradiation (Le) in the inspiration phase, respectively. Thirty subjects participated in this study. The diaphragm was used as the tracking target, and time-dependent changes in the position of the target were measured together with those in the respiratory signal level. For each subject, the following maps were created by varying the combination of Ls and Le: absolute target displacement (ATD) map, relative target displacement (RTD) map, and gate-on duty cycle (GDC) map. By classifying respiratory signal waveforms, three respiratory types were derived (A: the length of end-expiration level >40% of a breathing cycle, B: the length of end-expiration level 20% of a breathing cycle, and C: the length of end-expiration level

Comparison of cerebral blood flow between perfusion computed tomography and xenon-enhanced computed tomography for normal subjects: territorial analysis.

OBJECTIVE: The purpose of this study was to clarify the difference between cerebral blood flow (CBF) by perfusion computed tomography (CT) and that by xenon-enhanced CT (Xe-CT) through simultaneous measurement. METHODS: Xenon-enhanced CT and perfusion CT were continually performed on 7 normal subjects. Ratios of CBF by perfusion CT (P-CBF) to CBF by Xe-CT (Xe-CBF) were measured for 5 arterial territories; 3 were territories of 3 major arteries (the anterior [ACA], middle [MCA], and posterior [PCA] cerebral arteries), and the other 2 were areas of the thalamus and putamen. RESULTS: The ratios were 1.30 +/- 0.10, 1.26 +/- 0.15, 1.61 +/- 0.15, 0.801 +/- 0.087, and 0.798 +/- 0.080 for the ACA, MCA, PCA, thalamus, and putamen, respectively. Although a good correlation was observed between P-CBF and Xe-CBF for each territory, the ratios were significantly different (P < 0.0001) between 3 territory groups (group 1: ACA and MCA, group 2: PCA, and group 3: thalamus and putamen). CONCLUSIONS: The difference in the ratio of P-CBF to Xe-CBF between the 3 territory groups was considered to result principally from the features of P-CBF. To evaluate P-CBF properly, its territorial characteristics should be taken into account.