Assessment of pancreatic blood flow with positron emission tomography and oxygen-15 water

Dynamic positron emission tomography (PET) was performed following an intravenous bolus injection of 15O-water for the assessment of regional pancreatic blood flow in 4 normal volunteers and 11 patients with pancreatic cancer. The regional pancreatic blood flow index (PFI) was calculated by the autoradiographic method assuming the time-activity curves of the aorta as an input function. The mean PFI value was 0.514 +/- 0.098 in the normal pancreas but it was decreased in pancreatic cancer (0.249 +/- 0.076) (p less than 0.01), with a concomitant decrease in the pancreatic region distal to the tumor. On the other hand, in cases with body or tail cancer, the part proximal to the tumor (nontumorous head region) had a similar PFI value (0.554 +/- 0.211) to that of normal cases. Thus, a PET study with 15O-water permits quantitative assessment of pancreatic blood flow which decreased in both pancreatic cancer and concomitant obstructive pancreatitis distal to the tumor.     

Quantitative assessment of regional myocardial blood flow using oxygen-15-labelled water and positron emission tomography: a multicentre evaluation in Japan

Recently, a method has been proposed for the quantitative measurement of regional myocardial blood flow (MBF) using oxygen-15-labelled water and positron emission tomography (PET). A multicentre project was organized with the intention of evaluating the accuracy of this method, particularly as a multicentre clinical investigative tool. Each of seven institutions performed PET studies on more than five normal volunteers following a specified protocol. The PET study included a transmission scan, a ¹⁵O-carbon monoxide static scan and a ¹⁵O-water dynamic scan, thereby yielding MBF values which should have been independent of the spatial resolution of the PET scanner employed. Fifty-three subjects (aged 20–63 years, mean±SD 36±12 years) were studied at rest, and 31 of these subjects were also studied after dipyridamole in five institutions. Inter-institution consistency and intra-subject variation in MBF values were then evaluated. MBF averaged for all subjects was 0.93±0.34 ml min^–1 g^–1 at rest and 3.40±1.73 ml min^–1 g^–1 after the administration of dipyridamole, and the flow reserve (defined as the ratio of the two MBF values) was 3.82±2.12; these values are consistent with previous reports. Resting MBF values were significantly correlated with the heart rate–blood pressure product (RPP) (y=0.31+6.56E^-5 x, P<0.010), and RPP was in resting MBF observed in all institutions was well explained by the age-dependent RPP. No significant difference was observed in resting MBF among the institutions. Except in one institution, no significant difference was seen in dipyridamole MBF or myocardial flow reserve. No significant difference was found among the myocardial segments. Regional variation was reasonably small in five institutions, but was not acceptable in two institutions, which was attributed to the scanner performance. These observations suggest that the ¹⁵O-water PET technique is useful for a multicentre clinical study if the PET scanner can provide time-activity data with good count statistics. Received 25 April and in revised form 30 August 1999     

Quantitative assessment of regional myocardial blood flow using oxygen-15-labelled water and positron emission tomography: a multicentre evaluation in Japan

Recently, a method has been proposed for the quantitative measurement of regional myocardial blood flow (MBF) using oxygen-15-labelled water and positron emission tomography (PET). A multicentre project was organized with the intention of evaluating the accuracy of this method, particularly as a multicentre clinical investigative tool. Each of seven institutions performed PET studies on more than five normal volunteers following a specified protocol. The PET study included a transmission scan, a 15O-carbon monoxide static scan and a 15O-water dynamic scan, thereby yielding MBF values which should have been independent of the spatial resolution of the PET scanner employed. Fifty-three subjects (aged 20-63 years, mean+/-SD 36+/-12 years) were studied at rest, and 31 of these subjects were also studied after dipyridamole in five institutions. Inter-institution consistency and intra-subject variation in MBF values were then evaluated. MBF averaged for all subjects was 0.93+/-0.34 ml min(-1) g(-1) at rest and 3.40+/-1.73 ml min(-1) g(-1) after the administration of dipyridamole, and the flow reserve (defined as the ratio of the two MBF values) was 3.82+/-2.12; these values are consistent with previous reports. Resting MBF values were significantly correlated with the heart rate-blood pressure product (RPP) (y=0.31+6.56E-5x, P<0.010), and RPP was in resting MBF observed in all institutions was well explained by the age-dependent RPP. No significant difference was observed in resting MBF among the institutions. Except in one institution, no significant difference was seen in dipyridamole MBF or myocardial flow reserve. No significant difference was found among the myocardial segments. Regional variation was reasonably small in five institutions, but was not acceptable in two institutions, which was attributed to the scanner performance. These observations suggest that the 15O-water PET technique is useful for a multicentre clinical study if the PET scanner can provide time-activity data with good count statistics.     

Measurement of myocardial blood flow with oxygen-15 labelled water: comparison of different administration protocols

Positron emission tomography (PET) in conjunction with C¹⁵O₂ or H₂ ¹⁵O can be used to measure myocardial blood flow (MBF) and tissue fraction (TF), i.e. the fraction of the tissue mass in the volume of the region of interest. However, with C¹⁵O₂ inhalation, the tissue fraction in the septum is overestimated. Bolus injection of H₂ ¹⁵O together with arterial cannulation gives very precise results but is invasive. The purpose of this study was to develop a method which circumvents these problems. A four-parameter model with parameters for MBF, TF and spill-over fractions from both left and right ventricular cavities was developed. This method was compared with a three-parameter model (no right ventricular cavity spill-over) in both septal and non-septal regions of interest for three different administration protocols: bolus injection of H₂ ¹⁵O, infusion of H₂ ¹⁵O and inhalation of C¹⁵O₂. It was found that MBF can be measured with intravenous administration of H₂ ¹⁵O without the requirement for arterial cannulation. The four-parameter protocol with bolus injection was stable in clinical studies. The four-parameter model proved essential for the septum, where it gave highly significantly better fits than did the three-parameter model (P<0.00003 in each of 15 subjects). Administration of H₂ ¹⁵O together with this four-parameter model also circumvented the problem of overestimation of TF in the septum seen with C¹⁵O₂ inhalation. In addition, the radiation dose of H₂ ¹⁵O protocols is lower than that of C¹⁵O₂ inhalation. Using a left atrial input curve instead of a left ventricular cavity input curve gave the same mean MBF and TF. Received 30 January and in revised form 8 April 1998     

Measurement of absolute bone blood flow by positron emission tomography

A method of measuring bone blood flow has been developed using ¹⁸F sodium fluoride and positron emission tomography. The blood flow levels are in line with those obtained experimentally from microsphere embolisation. This investigative method could be applied to elucidate a number of clinical questions involving bone perfusion.     

Quantitative measurement of myocardial blood flow with oxygen-15 water and positron computed tomography: an assessment of potential and problems

An in vivo measurement technique using 15O water and positron CT for quantitation of myocardial blood flow (MBF) was investigated. A closed-chest dog model and NeuroECAT scanner were used in the study. The in vivo technique involves i.v. infusion of 15O water for a duration of 2-3 min. Oxygen-15 water radioactivity in myocardium was imaged with a NeuroECAT scanner for 10 min, starting at the time of tracer infusion. A separate scan following inhalation of 15O CO was obtained to label the blood pool and to help remove the contribution of radioactivity in the blood pool during the 15O water scans. The integrated projection technique was used for calculating MBF. The quantitative microsphere technique for measurement of MBF was performed along with the 15O water study to provide reference values, with which the MBF values by the in vivo technique was compared. Results of 12 experimental runs (in seven animals) show the in vivo technique with 15O water and positron CT can give quantitative flow images of myocardium. The in vivo positron CT measurement was found to correlate well (r = 0.93) with the in vitro values (by microspheres) over the flow range of 40 to 150 ml/min/100 g.     

A new subtraction method for obtaining myocardial perfusion images with oxygen-15 water and positron emission tomography

The myocardial positron emission tomograms which are obtained during the perfusion phase following bolus injection of O-15 water (H2(15)O) intravenously require subtraction of the blood pool activity overlaid upon the myocardium. Subtraction has been carried out using the blood pool images obtained in the same position following single inhalation of O-15 labeled carbon monoxide gas (C15O). However, because a difference in activity exists between the left ventricular (LV) cavity and the right ventricular (RV) cavity, simple subtraction of the LV cavity activity using C15O blood pool images induced significant over-subtraction in the right-side heart including the interventricular septum and RV wall. We developed a new method, "two-component subtraction," in which the C15O blood pool images were decomposed into the right-side and left-side components using the early phase images of the H2(15)O dynamics under the assumption that the whole activity of that phase was distributed in the right-side heart homogeneously. Thus we subtracted the blood pool spillover from RV and LV separately. This method provided myocardial perfusion images of high quality which were well correlated with N-13 ammonia images.     

Reproducibility of repeated human regional splenic blood flow measurements using [15O] water and positron emission tomography.

The reproducibility of measurement of regional splenic blood flow by dynamic positron emission tomography (PET) using [15O]water was evaluated. In 19 patients, the correlation between the first and second of two serial dynamic measurements was significant (P=1.78 x 10(-6); r=0.858). The regression equation was y = 1.06x, and the slope of the line described had a 95% confidence interval of 0.09. The error apparent between the two measurements was 0.129 (95% confidence interval 0.059). The results demonstrated sufficiently good reproducibility for measurements of regional splenic blood flow with PET and [15O]water to suggest use of this method for serial measurements intended to detect change, including drug effects.     

Measurement of cerebral blood flow with a bolus of oxygen-15-labelled water: Comparison of dynamic and integral methods

A method is presented for the measurement of cerebral blood flow (CBF) with a bolus of water labelled with oxygen 15. The method, which has been evaluated in normal volunteers, is based on Kety's model, with two additional parameters to account for the difference in the time of tracer arrival in the radial and carotid arteries (delay) and for dispersion of the tracer in the body and/or blood counting systems. It combines the advantages of: (i) dynamic data collection for estimation of delay and dispersion; (ii) robustness and linearity of CBF estimates with an integral method; and (iii) simplicity of continuous external monitoring of arterial blood radioactivity, particularly with repeated measurements. An optimized protocol is proposed for routine applications in neurological and neurophysiological studies.     

Measurement of cerebral blood flow with a bolus of oxygen-15-labelled water: comparison of dynamic and integral methods

A method is presented for the measurement of cerebral blood flow (CBF) with a bolus of water labelled with oxygen 15. The method, which has been evaluated in normal volunteers, is based on Kety's model, with two additional parameters to account for the difference in the time of tracer arrival in the radial and carotid arteries ("delay") and for dispersion of the tracer in the body and/or blood counting systems. It combines the advantages of: (i) dynamic data collection for estimation of delay and dispersion; (ii) robustness and linearity of CBF estimates with an integral method; and (iii) simplicity of continuous external monitoring of arterial blood radioactivity, particularly with repeated measurements. An optimized protocol is proposed for routine applications in neurological and neurophysiological studies.     

Preparation of oxygen-15 butanol for positron tomography

Butanol was labeled with 15O using the reaction of tri-n-butyl borane with oxygen gas. The carrier-added synthesis and purification was accomplished in 4 min from the end of bombardment. The efficiency of radiolabel incorporation was 50%. The procedure described will produce [15O]butanol in an amount and quality sufficient for positron tomographic use. This compound is immediately useful for blood flow measurement based upon previous validation of butanol labeled with other radionuclides for that purpose.     

Brain oxygen utilization measured with oxygen-15 radiotracers and positron emission tomography: generation of metabolic images

We recently described a PET method for the measurement of local brain tissue oxygen extraction (E) and the local cerebral metabolic rate for oxygen (CMRO2) using 15O-labeled radiotracers. The equation for the calculation of E from measured PET data is mathematically complex and its direct application in the generation of PET images of either E or the CMRO2 on a pixel-by-pixel basis is computationally burdensome. We describe a simplification of this equation which permits the efficient generation of quantitative images.     

Clinical measurement of blood flow in tumours using positron emission tomography: a review

In oncology drug development there is an increasing need for the in vivo physiological measurement of changes in tumour blood flow in response to therapy. Positron Emission Tomography (PET) is being increasingly used in oncology patients to measure blood flow. Here we review the clinical use of PET to measure vascular parameters in man.     

Measurement of human blood brain barrier integrity using 11C-inulin and positron emission tomography

Positron emission tomography (PET) using ¹¹C-inulin was demonstrated to be applicable to the clinical measurement of blood brain barrier permeability and cerebral interstitial fluid volume. Kinetic data were analyzed by application of a two compartment model, in which blood plasma and interstitial fluid spaces constitute the compartments. The blood activity contribution was subtracted from the PET count with the aid of the ¹¹CO inhalation technique. The values we estimated in a human brain were in agreement with the reported values obtained for animal brains by the use of ¹⁴C-inulin.     

Measurement of human blood brain barrier integrity using 11C-inulin and positron emission tomography

Positron emission tomography (PET) using 11C-inulin was demonstrated to be applicable to the clinical measurement of blood brain barrier permeability and cerebral interstitial fluid volume. Kinetic data were analyzed by application of a two compartment model, in which blood plasma and interstitial fluid spaces constitute the compartments. The blood activity contribution was subtracted from the PET count with the aid of the 11CO inhalation technique. The values we estimated in a human brain were in agreement with the reported values obtained for animal brains by the use of 14C-inulin.     

Use of the left ventricular time-activity curve as a noninvasive input function in dynamic oxygen-15-water positron emission tomography.

Noninvasive recording of arterial input functions using regions of interest (ROIs) in the left ventricular (LV) chamber obviates the need for arterial cannulation in PET, but it is compromised by the limited recovery coefficient of the LV chamber and by statistical noise. In the present study, a new mathematical model has been developed, which corrects for the spillover of radioactivity both from the myocardium into the LV ROI and the blood into the myocardial ROI. The method requires the measurement of a time-activity curve in the LV chamber during the dynamic H2(15)O PET study and the measurement of the recovery coefficient of the LV ROI using a 15O-carbon monoxide (C15O) scan and venous blood sampling. This approach was successfully validated against direct measurements of the arterial input function using an on-line beta detector in five greyhounds undergoing dynamic H2(15)O PET imaging. This technique also yielded myocardial blood flow (MBF) values which were not significantly different from those obtained with the beta-probe analyses (maximum difference less than 2%), provided that the LV ROIs were sufficiently large to provide good counting statistics. When this model was not applied for large ROIs (small recovery in LV ROI), systematic overestimations in MBF compared with beta-probe analysis (e.g., a factor by 40% for a recovery coefficient of 0.7) were observed. Thus, this technique enabled the prediction of an accurate input function using the LV time-activity curve, and hence, noninvasive quantification of MBF without arterial cannulation.     

Measurement of regional cerebral blood flow and oxygen utilisation in patients with cerebral tumours using 15O and positron emission tomography: Analytical techniques and preliminary results

Summary Regional cerebral blood flow and oxygen utilisation have been studied in 8 patients with brain tumours using continuous inhalation of C¹⁵O₂ and ¹⁵O₂ and positron emission tomography. The methods used to analyse the regional cerebral pathophysiology are presented. A relative uncoupling between oxygen consumption and blood flow was observed in all tumours as indicated by a decreased regional fractional extraction of oxygen (rOER). This suggests that a major proportion of these tumours had sufficient blood supply to meet oxygen metabolic demand. A decrease of blood flow in grey matter was found both in the affected and contralateral hemispheres of the brain. Matched reductions of flow and oxygen utilisation were observed in oedematous tissue.     

Quantitative cerebral blood flow measurement with dynamic perfusion CT using the vascular-pixel elimination method: comparison with H2(15)O positron emission tomography

BACKGROUND AND PURPOSE: Blood vessels are usually conspicuous on dynamic CT perfusion images. The presence of large vessels may lead to overestimation of the quantitative value of cerebral blood flow (CBF). We evaluated the efficacy of the vascular-pixel elimination (VPE) method in quantitative CT perfusion imaging, in comparison with positron emission tomography (PET). METHODS: Five healthy volunteers underwent CT perfusion and PET studies. A four-channel multi-detector row CT scanner was used. Dynamic cine scanning was performed after bolus injection of an intravenous contrast agent. CT-CBF was calculated by the central volume principle and deconvolution method. PET was performed after infusion of (15)O-labeled water. PET-CBF was calculated by using a nonlinear least squares method. Average CBF values of the whole section, gray matter, and white matter with both CT and PET were compared after image registration. The comparison was performed with and without VPE. In the VPE method, the vascular pixels were defined by the cerebral blood volume value of the pixel. The threshold of VPE was changed from 5 to 20 mL/100 g. Pixel-by-pixel correlation between CT-CBF and PET-CBF and linear regression analysis were also performed. RESULTS: Without VPE, CT-CBF was overestimated in all subjects. As the VPE threshold decreased, CT-CBF decreased and the correlation coefficient increased. The best correlation was observed at a VPE threshold of 8 mL/100 g in four of the five subjects. Average CT-CBF values, without VPE, of the whole section, gray matter, and white matter were 59.01, 66.73, and 42.53 mL/100 g/min, respectively. With VPE (threshold, 8 mL/100 g), average CT-CBF values of the whole section, gray matter, and white matter were 45.56, 52.75, and 30.38, respectively. The corresponding PET-CBF values were 46.86, 50.89, and 38.20 mL/100 g/min, respectively. CONCLUSION: Vascular pixels should be excluded from the calculation of CT-CBF to avoid overestimation of the CBF values. If vascular pixels are excluded, CBF calculation with CT perfusion imaging is considerably accurate.