Validation of PET-acquired input functions for cardiac studies

To validate the determination of the arterial input function by noninvasive dynamic PET imaging, measurements of blood-pool activity in canine LV by PET were compared to beta probe measurements of arterial blood withdrawn directly from the LV. PET scans were done during intravenous bolus injections of [13N]ammonia or 82Rb, while the activity of blood withdrawn continuously from a catheter inserted in the LV was measured with a beta probe. PET determinations of LV blood-pool activity were compared with dispersion-corrected beta probe time-activity curves. In 15 experiments involving four dogs under a wide range of physiologic conditions, LV time-activity curves obtained with PET matched well in shape with those obtained with the beta probe. Linear regression yielded slopes within 10% of unity (95% confidence interval) and high correlation (r greater than 0.968, p less than 0.001). We conclude that noninvasive measurement of the arterial input function by dynamic PET imaging is valid.     

Liver kinetics of glucose analogs measured in pigs by PET: importance of dual-input blood sampling.

Metabolic processes studied by PET are quantified traditionally using compartmental models, which relate the time course of the tracer concentration in tissue to that in arterial blood. For liver studies, the use of arterial input may, however, cause systematic errors to the estimated kinetic parameters, because of ignorance of the dual blood supply from the hepatic artery and the portal vein to the liver. METHODS: Six pigs underwent PET after [15O]carbon monoxide inhalation, 3-O-[11C]methylglucose (MG) injection, and [18F]FDG injection. For the glucose scans, PET data were acquired for 90 min. Hepatic arterial and portal venous blood samples and flows were measured during the scan. The dual-input function was calculated as the flow-weighted input. RESULTS: For both MG and FDG, the compartmental analysis using arterial input led to systematic underestimation of the rate constants for rapid blood-tissue exchange. Furthermore, the arterial input led to absurdly low estimates for the extracellular volume compared with the independently measured hepatic blood volume of 0.25 +/- 0.01 mL/mL (milliliter blood per milliliter liver tissue). In contrast, the use of a dual-input function provided parameter estimates that were in agreement with liver physiology. Using the dual-input function, the clearances into the liver cells (K1 = 1.11 +/- 0.11 mL/min/mL for MG; K1 = 1.07 +/- 0.19 mL/min/mL for FDG) were comparable with the liver blood flow (F = 1.02 +/- 0.05 mL/min/mL). As required physiologically, the extracellular volumes estimated using the dual-input function were larger than the hepatic blood volume. The linear Gjedde-Patlak analysis produced parameter estimates that were unaffected by the choice of input function, because this analysis was confined to time scales for which the arterial-input and dual-input functions were very similar. CONCLUSION: Compartmental analysis of MG and FDG kinetics using dynamic PET data requires measurements of dual-input activity concentrations. Using the dual-input function, physiologically reasonable parameter estimates of K1, k2, and Vp were obtained, whereas the use of conventional arterial sampling underestimated these parameters compared with independent measurements of hepatic flow and hepatic blood volume. In contrast, the linear Gjedde-Patlak analysis, being less informative but more robust, gave similar parameter estimates (K, V) with both input functions.     

The reproducibility of independently measuring human regional hepatic arterial,portal and total hepatic blood flow using [15O]water and positron emission tomography

The reproducibility of repeated human regional hepatic blood flow quantification using [15O]water and positron emission tomography (PET) was evaluated as a method of monitoring the effect of drug administration on hepatic blood flow. Nineteen patients underwent two measurements of hepatic blood flow by PET. Fifteen minutes after the first dynamic study using [15O]water, a second dynamic study was performed, and hepatic blood flow was calculated. The correlation between the first and second dynamic study of arterial blood flow was highly significant (P=6.31 x 10(-10), r=0.946). The regression line was y=1.08x. The mean error between studies was 0.158. The correlation between the first and second dynamic study of portal blood flow also was significant (P=1.29 x 10(-7), r=0.897). The regression line was y=1.03x. The mean error between the studies was 0.164. The correlation between total hepatic blood flow in the first and second dynamic study, too, was significant (P=2.68 x 10(-7), r=0.888). The regression line was defined by y=1.06x. The mean error between studies was 0.140. Hepatic blood flow has increased if the second measurement of hepatic arterial, portal, and total blood flow is more than 115%, 111% and 114% of baseline, and has decreased if the second measurement is less than 101%, 95% and 98% of the first measurement.     

Use of technetium-99m-MAG3 for renal scintigraphy after angiotensin-converting enzyme inhibition.

Technetium-99m-mercaptoacetyltriglycine (99mTc-MAG3) was tested in 82 hypertensive patients submitted to renal scintigraphy 1 hr after oral premedication with 50 mg of Captopril. Baseline studies were obtained only for those patients showing abnormal findings in the provocative study. All patients underwent renal arteriography. Sensitivity and specificity for the detection of renal artery stenosis (RAS) greater than 50% were 89% and 91%, respectively. After Captopril administration, tracer parenchymal transit time increased significantly in ischemic kidneys (334 +/- 93 sec in baseline conditions versus 468 +/- 96 sec after Captopril, p less than 0.001) but not in kidneys with no RAS or RAS less than 50% (243 +/- 46 sec versus 271 +/- 95 sec, p = ns). False-positive responses were mostly bilateral and associated with a marked decrease in blood pressure. Technetium-99m-MAG3 is an effective compound for detecting RAS greater than or equal to 50% with Captopril renal scintigraphy. Performing the provocative test as a first step considerably reduced the number of scintigraphic studies required.     

Perfusion CT compared to H<Subscript>2</Subscript><Superscript>15</Superscript>O/O<Superscript>15</Superscript>O PET in patients with chronic cervical carotid artery occlusion

INTRODUCTION: The purpose of this study was to compare the results of perfusion computed tomography (PCT) with those of (15)O(2)/H(2) (15)O positron emission tomography (PET) in a subset of Carotid Occlusion Surgery Study (COSS) patients. MATERIALS AND METHODS: Six patients enrolled in the COSS underwent a standard-of-care PCT in addition to the (15)O(2)/H(2) (15)O PET study used for selection for extracranial-intracranial bypass surgery. PCT and PET studies were coregistered and then processed separately by different radiologists. Relative measurement of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were calculated from PET. PCT datasets were processed using different arterial input functions (AIF). Relative PCT and PET CBF values from matching regions of interest were compared using linear regression model to determine the most appropriate arterial input function for PCT. Also, PCT measurements using the most accurate AIF were evaluated for linear regression with respect to relative PET OEF values. RESULTS: The most accurate PCT relative CBF maps with respect to the gold standard PET CBF were obtained when CBF values for each arterial territory are calculated using a dedicated AIF for each territory (R (2) = 0.796, p < 0.001). PCT mean transit time (MTT) is the parameter that showed the best correlation with the count-based PET OEF ratios (R (2) = 0.590, p < 0.001). CONCLUSION: PCT relative CBF compares favorably to PET relative CBF in patients with chronic carotid occlusion when processed using a dedicated AIF for each territory. The PCT MTT parameter correlated best with PET relative OEF.     

Hepatic enhancement in multiphasic contrast-enhanced MDCT: comparison of high- and low-iodine-concentration contrast medium in same patients with chronic liver disease

OBJECTIVE: The aim of this study was to evaluate the degree of hepatic enhancement and image quality in patients with cirrhosis or chronic hepatitis who underwent multiphasic contrast-enhanced dynamic imaging on MDCT at least twice using standard (300 mg I/mL) and higher (370 mg I/mL) iodine concentrations in contrast medium during follow-up periods. MATERIALS AND METHODS: This study included 20 patients with chronic liver diseases who underwent at least two multiphasic contrast-enhanced dynamic MDCT examinations using 100 mL of standard (300 mg I/mL = group A) and higher (370 mg I/mL = group B) iodine concentrations in contrast medium. After we obtained unenhanced CT scans, we performed multiphasic scanning at 30 sec (arterial phase), 60 sec (portal phase), and 180 sec (late phase) after the start of contrast medium injection. The CT values of hepatic parenchyma, abdominal aorta, and portal vein were measured. The mean enhancement value was defined as the difference in CT values between unenhanced and contrast-enhanced images. Visual image quality was also assessed on the basis of the degree of hepatic and vascular enhancement, rated on a 4-point scale. RESULTS: The mean hepatic parenchyma enhancement values in group B was significantly greater (p < 0.001) than those in group A during the portal phase (43.8 +/- 8.2 H vs 36.2 +/- 7.3 H) and the late phase (33.7 +/- 7.0 H vs 27.3 +/- 3.9 H), but the difference on the arterial phase images between the two groups (9.4 +/- 3.2 H vs 8.3 +/- 2.5 H) was not significant. The mean aorta-to-liver contrast during the arterial phase in group B was significantly higher (p < 0.001) than that in group A (236 +/- 40 H vs 193 +/- 32 H). For qualitative analysis, the mean visual scores for hepatic parenchyma and vasculature enhancement in group B were significantly higher than those in group A in arterial phase (p < 0.018), portal phase (p < 0.0001), and late phase (p < 0.0001). CONCLUSION: In the same patients with chronic liver diseases, a higher iodine concentration (370 mg I/mL) in the contrast medium improves contrast enhancement of liver parenchyma in the portal phase and late phase images, improves overall image quality, and helps improve diagnostic accuracy for liver diseases on multiphasic contrast-enhanced dynamic MDCT.     

Bringing physiology into PET of the liver

Several physiologic features make interpretation of PET studies of liver physiology an exciting challenge. As with other organs, hepatic tracer kinetics using PET is quantified by dynamic recording of the liver after the administration of a radioactive tracer, with measurements of time-activity curves in the blood supply. However, the liver receives blood from both the portal vein and the hepatic artery, with the peak of the portal vein time-activity curve being delayed and dispersed compared with that of the hepatic artery. The use of a flow-weighted dual-input time-activity curve is of importance for the estimation of hepatic blood perfusion through initial dynamic PET recording. The portal vein is inaccessible in humans, and methods of estimating the dual-input time-activity curve without portal vein measurements are being developed. Such methods are used to estimate regional hepatic blood perfusion, for example, by means of the initial part of a dynamic (18)F-FDG PET/CT recording. Later, steady-state hepatic metabolism can be assessed using only the arterial input, provided that neither the tracer nor its metabolites are irreversibly trapped in the prehepatic splanchnic area within the acquisition period. This is used in studies of regulation of hepatic metabolism of, for example, (18)F-FDG and (11)C-palmitate.     

Quantification of [(18)F]FDG uptake in the normal liver using dynamic PET: impact and modeling of the dual hepatic blood supply.

For quantification of hepatic [(18)F]FDG uptake, the dual blood supply to the liver must be considered. In contrast to the arterial input, however, the portal venous blood supply to the liver cannot be monitored directly by PET because of the inaccessibility of the portal vein on PET scans. In this study, we investigated whether the dual hepatic input can be predicted from the measurable arterial input. Moreover, we assessed the effect of different input models on the rate constants of the standard 3-compartment model describing regional uptake of FDG. METHODS: Dynamic FDG PET scanning was performed on 5 foxhounds. Activity concentrations in blood from the aorta and the portal vein were measured simultaneously using external circuits. After image reconstruction, time--activity courses were determined from the aorta and the liver. The venous input was approximated by convolving the arterial input with a notional system function describing the dispersion of the arterial input on its way through the gastrointestinal tract. On the basis of these data, 5 different hepatic input models, which pertain to a single-input as well as a dual-input scenario, were statistically compared with regard to the adequacy of the model fits to liver data and to differences in the estimated rate constants. RESULTS: Portal venous input to the liver could be approximated by convolving the arterial input function with a system function. From this function, a mean transit time of 25 s was computed for FDG to pass through the gastrointestinal tract. According to the statistical analysis, dual-input models were superior to their single-input counterparts. However, differences in the rate constants estimated for the 5 input models were in the same order as interindividual variations within the different model groups. For the dephosphorylation rate constant, a consistent value of 0.05 +/- 0.01 min(-1) was found. CONCLUSION: Dual-input models proved to be superior to single-input models with respect to the adequacy of FDG model fits to normal liver data. However, the hepatic blood supply may be approximated by the arterial input function as well, especially for the evaluation of liver lesions mainly fed by the hepatic artery.     

The utility of SPECT for 99mTc-MAA hepatic arterial perfusion scintigraphy

The utility of single-photon emission computed tomography (SPECT) for hepatic arterial perfusion scintigraphy was evaluated in 86 patients (91 studies). Previous reports have shown planar studies to be valuable for the clinical management of patients receiving intraarterial chemotherapy and more reliable than angiography in determining blood flow distribution. However, overlying areas of intra- and extrahepatic perfusion can sometimes make interpretation of these two-dimensional images difficult. Since SPECT has the potential to depict the three-dimensional distribution of perfusion, separate out overlying activity, and improve contrast resolution, SPECT Tc-MAA perfusion studies were compared to planar studies. Planar and SPECT studies both demonstrated the extent of hepatic and tumor perfusion, although occasionally SPECT added additional information. SPECT was most useful in confirming or excluding extrahepatic perfusion that was suspected but not definite on planar studies. Extrahepatic abdominal perfusion was found to be present in 11 (12%) of 91 studies. All patients with confirmed extrahepatic perfusion who received intraarterial chemotherapy had symptoms of drug toxicity compared to only a 23% incidence in those without evidence of extrahepatic perfusion (p less than 0.001). This report demonstrates that SPECT can improve the qualitative interpretation of hepatic arterial perfusion studies.     

Assessment of the splanchnic vascular capacity and capacitance using quantitative equilibrium blood-pool scintigraphy

A series of human and animal experiments were carried out to assess the usefulness of equilibrium blood pool scintigraphy (EBPS) to study acute changes of the splanchnic vascular capacity and the splanchnic vascular pressure-volume (P-V) relationship. Corrected regional abdominal count rate changes, before and after various pharmacologic interventions, were used to assess regional splanchnic vascular volume changes. Animals were instrumented to manipulate and record splanchnic venous pressures. In patients, splanchnic vascular capacity increased by 5.2 +/- 6.9% (p less than 0.001) after 0.6 mg sublingual nitroglycerin while no significant change was noted after sugar pills (0.9 +/- 5.2%, p greater than 0.3). In dogs, splanchnic vascular capacity decreased by a mean of 16% during infusion of angiotensin (p less than 0.001) and increased by a mean of 32% during infusion of nitroprusside (p less than 0.001). The splanchnic vascular P-V curve was shifted rightwards during nitroglycerin administration. Thus, using the radionuclide technique we detected the expected qualitative and quantitative shifts in splanchnic capacity and capacitance. We conclude that EBPS is a useful method to assess acute changes of 1) the splanchnic vascular P-V relationship, in invasive animal studies, and 2) the splanchnic vascular capacity in noninvasive human and animal studies.     

Renal vein Doppler sonography of obstructive uropathy

OBJECTIVE: Obstructive uropathy in the early stages can be difficult to diagnose using either standard sonography or the arterial resistive index. We tested the hypothesis that acute obstruction of the renal collecting system reduces the intraparenchymal renal compliance, which affects the intraparenchymal venous blood flow to a greater degree than the arterial flow. SUBJECTS AND METHODS: Twelve patients with clinical evidence of acute obstructive uropathy were referred for helical CT to confirm the diagnosis and to provide a gold standard by which we could evaluate the sonographic findings in the 12 test patients. Twelve patients without renal disease served as a control group. Doppler sonography of the interlobar arteries and veins of both kidneys then was performed, with the sonographer unaware of which kidney had an obstruction. Peak venous flow measurements and arterial resistive and venous impedance indexes were obtained. The impedance indexes of the obstructed and unobstructed kidney were compared for each patient. RESULTS: The mean arterial resistive indexes of the obstructed kidneys were larger than those of the unobstructed kidneys, 0.67 +/- 0.08 and 0.62 +/- 0.05, respectively (p = 0.05). The venous impedance indexes comparing obstructed and unobstructed sides were 0.38 +/- 0.25 and 0.80 +/- 0.25, respectively, a statistically significant result (p = 0.0002). On average, the peak venous flow signal in the obstructed kidney was 69% higher than that of the unobstructed kidney (p = 0.04) and 86% higher than that of the peak venous flow signal in the control group (p = 0.005). CONCLUSION: Renal obstruction alters the venous flow to a greater extent than the arterial flow, and a comparison between the venous flow in the obstructed and unobstructed kidneys may improve diagnostic accuracy.     

Use of arterialised venous instead of arterial blood for measurement of myocardial glucose metabolism during euglycaemic-hyperinsulinaemic clamping

Sampling of arterialised venous blood (AVB) is often used as an alternative to sampling of arterial blood when determining the myocardial metabolic rate of glucose (MRGlu). This method, however, has not yet been validated for measurement of plasma fluorine-18 fluorodeoxyglucose (FDG) activity during a euglycaemic-hyperinsulinaemic clamp (EHC). In this study, dynamic FDG scans were performed with arterial blood sampling during EHC. Samples of arterial and AVB or venous blood were simultaneously withdrawn at five time points for measurement of FDG activity and plasma glucose in 36 patients. Both venous to arterial and AVB to arterial ratios were calculated for FDG activity and plasma glucose. Mean ratios between AVB and arterial FDG activity were then used to create calculated arterialised venous input functions from corresponding arterial input functions. The mean effect of arterialisation on the calculation of K(i) was assessed. In nine additional patients, K(i) obtained with continuous sampling of AVB was compared with K(i) obtained with a corresponding (quality-controlled) image-derived input function from the ascending aorta. Using AVB, measurements of FDG activity were much more reliable than with venous blood sampling. As compared with arterial sampling, however, FDG activity was underestimated early after injection, while it was overestimated after 20 min. In both analyses, AVB resulted in approximately 10%+/-10% overestimation of K(i). Because of a 5%+/-5% underestimation of plasma glucose concentration with AVB, the net effect on the final calculation of MRGlu was small (on average 5% overestimation). It is concluded that the use of AVB has a small average effect on the determination of MRGlu. This method does, however, contribute to variability in the results. This variability cannot be explained by different degrees of arterialisation.     

Measurement of hepatic blood flow by use of per-rectal portal scintigraphy with 133Xe.

A relatively noninvasive method is needed to evaluate the hepatic blood flow of patients with liver disease. We used per-rectal portal scintigraphy with 133Xe, and analysed the time-activity curves of the liver and portal vein. To do this, wash-out curves of the liver were plotted, and the hepatic blood flow and the ratio of the blood flow to the right lobe of the liver to that to the left lobe (R/L ratio) were calculated. The mean hepatic blood flow was 137 +/- 23 ml/100 g/min for four patients with fatty liver, 139 +/- 16 ml/100 g/min for seven patients with chronic persistent hepatitis, 120 +/- 15 ml/100 g/min for ten patients with chronic aggressive hepatitis, and 75 +/- 21 ml/100 g/min for 14 patients with cirrhosis. All seven patients with hepatic blood flow that was less than 100 ml/100 g/min and an R/L ratio less than 1.0 had cirrhosis. Only two of the 22 patients with hepatic blood flow that was greater than 100 ml/100 g/min and an R/L ratio greater than 1.0 had cirrhosis. Per-rectal portal scintigraphy can be used to measure the hepatic blood flow, but it was not useful for the diagnosis of fatty liver.     

Hepatic blood flow in patients treated by continuous hepatic artery infusion chemotherapy]

Hepatic blood flow in tumor and nontumor regions was studied in four patients with hepatocellular carcinoma and in 16 patients with metastatic liver tumors. The regional hepatic blood flow was measured with the tissue clearance of 133Xe delivered through the implantable drug infusion system. The regional hepatic arterial/portal blood flow ratio was also measured by means of intravenous injection of 99mTc-stannous phytate. Mean hepatic arterial blood flow ratio of tumor regions was higher than that of nontumor regions (81.83 +/- 24.55% vs. 46.64 +/- 20.05%; p less than 0.01). This result suggests that hepatic arterial blood flow is increased in tumor regions of the liver. In tumor regions, the regional blood flow of the hepatic artery was inversely correlated with the mass reduction rate. In the lesions that showed a higher mass reduction rate by the continuous drug infusion treatment, the endothelial damage of the arterial wall and tumor necrosis seem to decrease blood flow. From this study, measurement of regional hepatic blood flow and hepatic arterial/portal blood flow ratio may be useful to evaluate the effectiveness of treatment for hepatic tumors.     

Quantitative measurement of oxygen metabolic rate in the rat brain using microPET imaging of briefly inhaled 15O-labelled oxygen gas

OBJECTIVE: The quantitative measurement of cerebral metabolic rate of oxygen (CMRO(2)) for rats using positron emission tomography (PET) has been technically difficult. The present study was performed to provide a technique to measure CMRO(2) for rats using a dedicated animal PET technique. METHODS: CMRO(2) in the rat brain was quantitatively measured under alpha-chloralose anaesthesia (30 mg . kg(-1) . h(-1), intravenous infusion) using a PET imaging technique. In our experiment, the (15)O-labelled gas tracer (O(15)O) was administered by a bolus insufflation into the lung through a surgically placed cannula in the trachea. The tracer distribution was then dynamically imaged using the microPET. Unlike other conventional PET methods in which a series of arterial blood samples need to be withdrawn for the measurement of an arterial input function, no arterial blood sampling was employed. Instead, the heart was scanned in dynamic mode at the same time of imaging the brain, and the region of interest drawn over the heart was analysed to obtain an arterial input function. RESULTS: The CMRO(2) value (micromol . 100 g(-1) . min(-1)) from 10 rats was 208 +/- 15 (mean +/- SD). CONCLUSIONS: Our results suggest that the microPET-based CMRO(2) measurement in the rat brain combined with a non-invasive measurement of arterial input function is promising, especially for many applications involving small animals in which repeated measurements of absolute CMRO(2) need to be performed.     

Factors influencing serial measurements of cardiac volumes by count-based methods: effects of elevated catecholamines, position, and exercise on technetium-99m-blood radioactivity concentration.

Most radionuclide methods for measuring cardiac volume require a determination of the blood radioactivity concentration. Thus, changes in blood radioactivity over time or during interventions might lead to spurious volume estimates unless blood radioactivity is serially measured. The effects of elevated epinephrine, posture and exercise on 99mTc-labeled blood radioactivity concentration were studied in 15 young (mean age = 28 yr) and 14 older (mean age = 68 yr) healthy males. An epinephrine infusion of 50 ng/kg/min resulted in a 4.1% +/- 1.0% increase in 99mTc-blood radioactivity (p less than or equal to 0.001) compared to baseline. Sitting increased blood radioactivity concentration by 12.3% +/- 3.0% (p less than 0.0002) compared to the supine position and peak supine bicycle exercise caused an 11.0% +/- 1.7% increase (p less than or equal to 0.0001) compared to supine rest. There was a significantly greater increase during peak supine exercise in the young compared to the older subjects (15.0% +/- 2.3% versus 6.3% +/- 2.0%, p less than or equal to 0.01). The mechanism of the increase in blood radioactivity concentration is uncertain, but presumably reflects the addition of hemoconcentrated red blood cells from the spleen and/or the loss of plasma volume. Failure to correct for the increased blood radioactivity concentration during exercise or pharmacological interventions will result in a significant error in serial measurements of cardiac volumes by methods requiring RBC radioactivity measurements.     

Value of a radionuclide limb blood flow technique in the assessment of percutaneous balloon and dynamic angioplasty.

In a prospective study, a radionuclide technique was used to evaluate the limb blood flow (LBF) changes in 30 patients undergoing dynamic (n = 15) or balloon (n = 15) angioplasty for arterial occlusions or stenoses, respectively. The results were compared with Doppler Ankle Brachial Index (DABI) and treadmill exercise tests. Whilst LBF values (ml of blood flow per 100 ml of limb volume per min) were significantly lower in limbs with arterial occlusion than stenosis (4.5 +/- 0.46 and 6.4 +/- 0.74, respectively; P less than 0.05). DABI provided no discrimination. Immediately after balloon angioplasty, there was a fall in DABI, from 0.60 +/- 0.05 to 0.47 +/- 0.04 (P less than 0.05), which rose 24 h later to 0.73 +/- 0.02 (P less than 0.01). Following dynamic angioplasty, DABI improved from 0.60 +/- 0.05 to 0.66 +/- 0.02 (P less than 0.05). At 3 weeks, the LBF improved from 4.6 +/- 0.66 to 11.1 +/- 0.53 (P less than 0.001) following dynamic angioplasty and from 6.2 +/- 0.68 to 8.53 +/- 0.81 (P less than 0.001) following balloon angioplasty. "Normal" LBF (greater than 10 ml/100 ml per min) was achieved in 80% of patients who underwent successful dynamic angioplasty but in only 36% of the balloon group (P less than 0.05, chi 2-test). Reproducibility of repeated LBF measurements in control limbs was superior to that of DABI. This was indicated by a lower coefficient of variation, 13.8% compared with 25.2%, and a higher correlation coefficient, r = 0.79 compared with 0.27. Treadmill exercise tests were invalid or impossible in 30% of all occasions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of liver blood flow using oxygen-15 labelled water and dynamic positron emission tomography: Limitations of model description

To date no satisfactory method has been available for the quantitative in vivo measurement of the complex hepatic blood flow. In this study two modelling approaches are proposed for the analysis of liver blood flow using positron emission tomography (PET). Five experiments were performed on three foxhounds. The anaesthetised dogs were each given an intravenous bolus injection of oxygen-15 labelled water, and their livers were then scanned using PET. Radioactivity in the blood from the aorta and portal vein was measured directly and simultaneously using closed external circuits. Time-activity curves were constructed from sequential PET data. Data analysis was performed by assuming that water behaves as a freely diffusible tracer and adapting the standard one-compartment blood flow model to describe the dual blood supply of the liver. Two particular modelling approaches were investigated: the dual-input model used both directly measured input functions (i.e. using the hepatic artery and the portal vein input, determined from the radioactivity detected in the aorta and portal vein respectively) whereas the single-input model used only the measured arterial curve and predicted the corresponding portal input function. Hepatic arterial flow, portal flow and blood volume were fitted from the PET data in several regions of the liver. The resulting estimates were then compared with reference blood flow measurements, obtained using a standard microsphere technique. The microspheres were injected in a separate experiment on the same dogs immediately prior to PET scanning. Whilst neither the single- nor the dual-input models accurately reproduced the arterial reference flow values, the flow values from the single-input model were closer to the microsphere flow values. The proposed single-input model would be a good approximation for liver blood flow measurements in man. The observed discrepancies between the PET and microsphere flow values may be due to the inherent temporal and spatial heterogeneity of liver blood flow. The results presented suggest that adaptation of the standard one-compartment blood flow model to describe the dual blood supply of the liver is limited and other flow tracers have to be considered for quantitative PET measurements in the liver.     

A noninvasive method for measuring portal venous/total hepatic blood flow by hepatosplenic radionuclide angiography

Radionuclide angiography was used to generate first-pass radioactivity vs. time curves for the left heart, right hepatic lobe, right lung, spleen, and both kidneys following rapid intravenous injection of 20 mCi (740 MBq) of 99mTc-pertechnetate. Seven normal subjects were examined as well as 57 cirrhotic patients, who also underwent angiographic grading of portal venous perfusion. For analysis, two time points were identified: (a) t0, when 99mTc first entered the liver (the initial rise of either curve); and (b)tc, when 99mTc was maximal in abdominal organs (the renal peak). Analysis was based on the slopes of the two phases of the hepatic curves t0 + 7 seconds and Tc + 7 seconds; this time selection permitted analysis of all curves. The hepatic perfusion index (HPI) = slope (tc + 7 secs)/slope (t0 + 7 secs) + slope (tc + 7 secs). The mean HPI for the normal subjects was 66% +/- 7; for the cirrhotic patients with angiographic Grades I, II, III, and IV, the HPI was 52% +/- 9, 37% +/- 6, 15% +/- 7, and 3% +/- 4, respectively. Correlation between HPI and angiography was significant (p less than 0.001). This method offers a readily available, rapid, relatively inexpensive, and quantitative method of grading the ratio of portal venous to total hepatic blood flow.