Absolute quantification of myocardial blood flow with 13N-ammonia and 3-dimensional PET.

The aim of this study was to compare 2-dimensional (2D) and 3-dimensional (3D) dynamic PET for the absolute quantification of myocardial blood flow (MBF) with (13)N-ammonia ((13)N-NH(3)). METHODS: 2D and 3D MBF measurements were collected from 21 patients undergoing cardiac evaluation at rest (n = 14) and during standard adenosine stress (n = 7). A lutetium yttrium oxyorthosilicate-based PET/CT system with retractable septa, enabling the sequential acquisition of 2D and 3D images within the same patient and study, was used. All 2D studies were performed by injecting 700-900 MBq of (13)N-NH(3). For 14 patients, 3D studies were performed with the same injected (13)N-NH(3) dose as that used in 2D studies. For the remaining 7 patients, 3D images were acquired with a lower dose of (13)N-NH(3), that is, 500 MBq. 2D images reconstructed by use of filtered backprojection (FBP) provided the reference standard for MBF measurements. 3D images were reconstructed by use of Fourier rebinning (FORE) with FBP (FORE-FBP), FORE with ordered-subsets expectation maximization (FORE-OSEM), and a reprojection algorithm (RP). RESULTS: Global MBF measurements derived from 3D PET with FORE-FBP (r = 0.97), FORE-OSEM (r = 0.97), and RP (r = 0.97) were well correlated with those derived from 2D FBP (all Ps < 0.0001). The mean +/- SD differences in global MBF measurements between 3D FORE-FBP and 2D FBP and between 3D FORE-OSEM and 2D FBP were 0.01 +/- 0.14 and 0.01 +/- 0.15 mL/min/g, respectively. The mean +/- SD difference in global MBF measurements between 3D RP and 2D FBP was 0.00 +/- 0.16 mL/min/g. The best correlation between 2D PET and 3D PET performed with the lower injected activity was found for the 3D FORE-FBP reconstruction algorithm (r = 0.95, P < 0.001). CONCLUSION: For this scanner type, quantitative measurements of MBF with 3D PET and (13)N-NH(3) were in excellent agreement with those obtained with the 2D technique, even when a lower activity was injected.     

Quantification of cerebral blood flow and oxygen metabolism with 3-dimensional PET and 15O: validation by comparison with 2-dimensional PET.

Quantitative PET with (15)O provides absolute values for cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF), which are used for assessment of brain pathophysiology. Absolute quantification relies on physically accurate measurement, which, thus far, has been achieved by 2-dimensional PET (2D PET), the current gold standard for measurement of CBF and oxygen metabolism. We investigated whether quantitative (15)O study with 3-dimensional PET (3D PET) shows the same degree of accuracy as 2D PET. METHODS: 2D PET and 3D PET measurements were obtained on the same day on 8 healthy men (age, 21-24 y). 2D PET was performed using a PET scanner with bismuth germanate (BGO) detectors and a 150-mm axial field of view (FOV). For 3D PET, a 3D-only tomograph with gadolinium oxyorthosilicate (GSO) detectors and a 156-mm axial FOV was used. A hybrid scatter-correction method based on acquisition in the dual-energy window (hybrid dual-energy window [HDE] method) was applied in the 3D PET study. Each PET study included 3 sequential PET scans for C(15)O, (15)O(2), and H(2)(15)O (3-step method). The inhaled (or injected) dose for 3D PET was approximately one fourth of that for 2D PET. RESULTS: In the 2D PET study, average gray matter values (mean +/- SD) of CBF, CBV, CMRO(2), and OEF were 53 +/- 12 (mL/100 mL/min), 3.6 +/- 0.3 (mL/100 mL), 3.5 +/- 0.5 (mL/100 mL/min), and 0.35 +/- 0.06, respectively. In the 3D PET study, scatter correction strongly affected the results. Without scatter correction, average values were 44 +/- 6 (mL/100 mL/min), 5.2 +/- 0.6 (mL/100 mL), 3.3 +/- 0.4 (mL/100 mL/min), and 0.39 +/- 0.05, respectively. With the exception of OEF, values differed between 2D PET and 3D PET. However, average gray matter values of scatter-corrected 3D PET were comparable to those of 2D PET: 55 +/- 11 (mL/100 mL/min), 3.7 +/- 0.5 (mL/100 mL), 3.8 +/- 0.7 (mL/100 mL/min), and 0.36 +/- 0.06, respectively. Even though the 2 PET scanners with different crystal materials, data acquisition systems, spatial resolution, and attenuation-correction methods were used, the agreement of the results between 2D PET and scatter-corrected 3D PET was excellent. CONCLUSION: Scatter coincidence is a problem in 3D PET for quantitative (15)O study. The combination of both the present PET/CT device and the HDE scatter correction permits quantitative 3D PET with the same degree of accuracy as 2D PET and with a lower radiation dose. The present scanner is also applicable to conventional steady-state (15)O gas inhalation if inhaled doses are adjusted appropriately.     

Mapping of local renal blood flow with PET and H(2)(15)O.

We developed a noninvasive method for the mapping of regional renal blood flow in humans using PET and H(2)(15)O. METHODS: Fifteen subjects participated in the study, 5 with normal renal function and 10 with renal disease. The protocol used a whole-body PET scanner, intravenous bolus injection of 1,110-1,850 MBq H(2)(15)O and sequential imaging at 3 s per frame. (131)I-Iodohippuran was used to independently assess effective renal plasma flow in each subject. Hippuran clearance and renal blood flow (RBF) were measured twice, before and after treatment with probenecid, to verify that RBF is not affected. Flow analysis was based on the Kety model, according to the operational equation: C(t) = F integral C(a)(u)du - k integral C(u)du, where F is the RBF, k is the tissue-to-blood clearance rate, C is the PET concentration, and C(a) is the tracer concentration in the abdominal aorta. F and k were estimated by linear least squares on a pixel-by-pixel basis to produce quantitative maps (parametric images) of RBF. The flow maps were analyzed by regions of interest (largely excluding the medulla and collecting system) for each kidney on each slice and pooled to yield mean RBF. RESULTS: In the 5 healthy subjects, mean RBF was 3.4 +/- 0.4 mL/min/g. There was no difference in flow between kidneys (t = -0.59; n = 11; P > 0.95). Before treatment with probenecid, RBF was linearly related to hippuran clearance (r(2) = 0.92). Probenecid treatment significantly reduced hippuran clearance (P < 0.003), but RBF was unchanged (P > 0.17). Compared with healthy control subjects, RBF was significantly decreased in patients with renal disease (P < 0.002). Flow maps were of good quality in all subjects, exhibiting characteristic patterns, with higher values in regions composed largely of renal cortex. CONCLUSION: Parametric mapping of RBF with PET and H(2)(15)O provides a straightforward, noninvasive method for quantitative mapping of RBF, which may prove useful in research applications and in the management of patients whose therapy alters renal tubular transport.     

H(2)(15)O PET validation of steady-state arterial spin tagging cerebral blood flow measurements in humans.

Steady-state arterial spin tagging approaches can provide quantitative images of CBF, but have not been validated in humans. The work presented here compared CBF values measured using steady-state arterial spin tagging with CBF values measured in the same group of human subjects using the H(2)(15)O IV bolus PET method. Blood flow values determined by H(2)(15)O PET were corrected for the known effects of incomplete extraction of water across the blood brain barrier. For a cortical strip ROI, blood flow values determined using arterial spin tagging (64+/-12 cc/100 g/min) were not statistically different from corrected blood flow values determined using H(2)(15)O PET (67+/-13 cc/100 g/min). However, for a central white matter ROI, blood flow values determined using arterial spin tagging were significantly underestimated compared to corrected blood flow values determined using H(2)(15)O PET. This underestimation could be caused by an underestimation of the arterial transit time for white matter regions.     

Measuring tumor blood flow with H(2)(15)O: practical considerations

The ability to measure blood flow to tumors non-invasively may be of importance in monitoring tumor therapies, assessing drug delivery, and understanding tumor physiology. Of all the radiotracer methods that have been proposed to measure tumor blood flow, the method based on labeled water-H(2)(15)O-may be the most applicable to tumors. It is highly diffusible, does not participate significantly in metabolic processes during the short times involved in the study, and its uptake and clearance can be easily modeled. We present here an analysis of the bolus injection water methodology and how it might best be used to monitor tumor blood flow. Several different formulations of the basic methodology, based on previous applications in the heart and brain, are discussed. Potential problems of adapting these previous methodologies to tumor blood flow are presented.     

Quantification of regional myocardial blood flow using dynamic H2(15)O PET and factor analysis.

Because the use of factor analysis has been proposed for extracting pure physiologic temporal or spatial information from dynamic nuclear medicine images, factor analysis should be capable of robustly estimating regional myocardial blood flow (rMBF) using H2(15)O PET without additional C15O PET, which is a cumbersome procedure for patients. Therefore, we measured rMBF using time-activity curves (TACs) obtained from factor analysis of dynamic myocardial H2(15)O PET images without the aid of C15O PET. METHODS: H2(15)O PET of six healthy dogs at rest and during stress was performed simultaneously with microsphere studies using 85Sr, 46Sc, and 113SN: We performed factor analysis in two steps after reorienting and masking the images to include only the cardiac region. The first step discriminated each factor in the spatial distribution and acquired the input functions, and the second step extracted regional-tissue TACS: Image-derived input functions obtained by factor analysis were compared with those obtained by the sampling method. rMBF calculated using a compartmental model with tissue TACs from the second step of the factor analysis was compared with rMBF measured by microsphere studies. RESULTS: Factor analysis was successful for all the dynamic H2(15)O PET images. The input functions obtained by factor analysis were nearly equal to those obtained by arterial blood sampling, except for the expected delay. The correlation between rMBF obtained by factor analysis and rMBF obtained by microsphere studies was good (r = 0.95). The correlation between rMBF obtained by the region-of-interest method and rMBF obtained by microsphere studies was also good (r = 0.93). CONCLUSION: rMBF can be measured robustly by factor analysis using dynamic myocardial H2(15)O PET images without additional C15O blood-pool PET.     

Direct comparison between 2-dimensional and 3-dimensional PET acquisition modes for myocardial blood flow absolute quantification with O-15 water and N-13 ammonia

BACKGROUND: Positron emission tomography scanners with retractable septa allow both 3-dimensional (3D) and 2-dimensional (2D) acquisition modes. The study aim was to directly compare 2D and 3D acquisition modes for the evaluation of absolute myocardial blood flow (MBF) over a wide range of flow values. METHODS AND RESULTS: Instrumentation was used in 4 dogs to reduce the left circumflex artery lumen by greater than 75%. During infusion of adenosine, MBF was measured with both 2D and 3D dynamic acquisition and both oxygen 15 water and nitrogen 13 ammonia. Injected activities were 333 MBq and 111 MBq for 2D acquisition and 3D acquisition, respectively. Data were reconstructed by analytic methods, and MBF was assessed by use of an 18-segment model. MBF values ranged from 0.4 to 5.8 mL x g(-1) x min(-1) with O-15 water and from 0.3 to 3.9 mL x g(-1) x min(-1) with N-13 ammonia. No significant differences were observed in absolute MBF values obtained with the 2 acquisition modes, regardless of the flow tracer used. Two-dimensionally and three-dimensionally derived MBF values were significantly strongly correlated by use of both O-15 water (y = 0.98x + 0.18, r = 0.87, P < .001) and N-13 ammonia (y = 0.99x + 0.09, r = 0.95, P < .001). CONCLUSION: Quantification of MBF in dogs with 3D positron emission tomography provides results similar to those obtained with the 2D technique, despite a lower activity being injected.     

Generation of parametric image of regional myocardial blood flow using H(2)(15)O dynamic PET and a linear least-squares method.

Although a parametric image of myocardial blood flow (MBF) can be obtained from H(2)(15)O PET using factor and cluster analysis, this approach is limited when factor analysis fails to extract each cardiac component. In this study, a linear least-squares (LLS) method for estimating MBF and generating a MBF parametric image was developed to overcome this limitation. The computer simulation was performed to investigate the statistical properties of the LLS method, and MBF values obtained from the MBF parametric images in dogs were compared with those obtained using the conventional region of interest (ROI) and invasive microsphere methods. METHODS: A differential model equation for H(2)(15)O in the myocardium was modified to incorporate the partial-volume and spillover effect. The equation was integrated from time 0 to each PET sampling point to obtain a linearlized H(2)(15)O model equation. The LLS solution of this equation was estimated and used to calculate the MBF, the perfusable tissue fraction (PTF), and the arterial blood volume fraction (V(a)). A computer simulation was performed using the input function obtained from canine experiments and the tissue time-activity curves contaminated by various levels of Poisson noise. The parametric image of the MBF, PTF, and V(a) was constructed using the PET data from dogs (n = 7) at rest and after pharmacologic stress. The regional MBF from the parametric image was compared with those produced by the ROI method using a nonlinear least-squares (NLS) estimation and an invasive radiolabeled microsphere technique. RESULTS: The simulation study showed that the LLS method was better than the NLS method in terms of statistical reliability, and the parametric images of the MBF, PTF, and V(a) using the LLS method had good image quality and contrast. The regional MBF values using the parametric image showed a good correlation with those using the ROI method (y = 0.84x + 0.40; r = 0.99) and the microsphere technique (y = 0.95x + 0.29; r = 0.96). The computation time was approximately 10 s for the 32 x 32 x 6 x18 (pixel x pixel x plane x frame) matrix. CONCLUSION: A noninvasive, very fast, and accurate method for estimating the MBF and generating a MBF parametric image was developed using the LLS estimation technique and H(2)(15)O dynamic myocardial PET.     

Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET.

The aim of this study was to evaluate the repeatability of endothelium-related myocardial blood flow (MBF) responses to cold pressor testing (CPT) as assessed by PET. METHODS: In 10 age-matched control subjects (26.6 +/- 3.4 y) and 10 tobacco smokers (24.9 +/- 3.3 y) MBF was assessed at rest and after repeated CPT (CPT1 and CPT2, 40 min apart) using PET with H(2)(15)O. CPT was performed by a 2-min immersion of the subject's foot in ice water. MBF values were corrected for cardiac workload (rate.pressure product), and the repeatability of CPT-related MBF values was assessed according to Bland and Altman. RESULTS: Corrected MBF at CPT1 and CPT2 were comparable in control subjects (1.79 +/- 0.37 vs. 1.70 +/- 0.35 mL/min/g; P = not significant [NS]) and in smokers (1.97 +/- 0.42 vs. 1.80 +/- 0.41 mL/min/g; P = NS). Repeatability coefficients in control subjects and smokers were 0.46 mL/min/g (27% of the mean MBF) and 0.51 mL/min/g (27%), respectively. MBF increased significantly after CPT in both groups but tended to be lower in smokers (P = 0.08). CONCLUSION: PET measured MBF combined with CPT is a feasible and repeatable method for the evaluation of endothelium-related changes of MBF.     

Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation

We have adapted the well-known tissue autoradiographic technique for the measurement of regional cerebral blood flow (CBF), originally proposed by Kety and his colleagues, for the measurement of CBF in human subjects using positron emission tomography (PET) and intravenously administered oxygen-15-labeled water. This report describes the steps necessary for the implementation of this PET/autoradiographic technique. In order to establish the accuracy of the method, we measured CBF with intravenously administered oxygen-15-labeled water and PET in anesthetized adult baboons and compared the results with blood flow measured by a standard tracer technique that uses residue detection of a bolus of oxygen-15-labeled water injected into the internal carotid artery. The correlation between CBF measured with PET and the true CBF for the same cerebral hemisphere was excellent. Over a blood-flow range of 10-63 ml/(min X 100 g), CBF (PET) = 0.90 CBF(true) + 0.40 (n = 23, r = 0.96, p less than 0.001). When blood flow exceeds 65 ml/(min X 100 g) CBF was progressively underestimated due to the known limitation of brain permeability to water.     

Calf flow reserve with H(2)(15)O PET as a quantifiable index of lower extremity flow.

Objective measures of recruitable blood flow are of importance in angiogenesis trials. We validated a new PET-derived flow reserve (FR) measurement in healthy subjects and subjects with peripheral artery disease (PAD). METHODS: Five healthy volunteers and 5 subjects with PAD underwent cannulation of the femoral artery and vein. Basal and maximal flow (100 micro g/kg/min of adenosine infused intraarterially) in the lower extremity was determined using thermodilution (TD) techniques. Subjects then underwent plethysmography (PL) followed by PET measurements of blood flow at the calf level. For the PET studies, a transmission scan followed by injection of 1.85 GBq (50 mCi) H(2)(15)O and dynamic scanning for 5 min were acquired in five 1-min frames. Regions of interest were drawn on successive PET image slices, and radioactivity was quantified from the first-minute scan after injection. FR for each of the 3 modalities was expressed as the ratio of adenosine to basal flow. RESULTS: PET-derived FR correlated strongly with TD (r = 0.82; P = 0.004) but not with PL (r = 0.17; P = 0.85). The mean average difference in FR between healthy volunteers and PAD subjects was 13.0 with PET and 4.5 with TD. The intra- and intersubject variability for PET expressed as the coefficient of variation was 10.5% and 29.0% for healthy subjects and 7.0% and 52.9% in PAD, respectively. CONCLUSION: As expected, FR was significantly lower in PAD subjects compared with healthy subjects as assessed with TD and PET but not with PL. PET-derived FR appears to be reproducible and generates sharper and higher indices of recruitable flow in healthy subjects and PAD. These findings have implications for the use of PET-derived FR as a sensitive index of recruitable flow in angiogenesis trials.     

Sequential H(2)(15)O PET studies in baboons: before and after amphetamine.

PET and (11)C-raclopride have been used to assess dopamine activity in vivo using a paradigm that involved d-amphetamine (AMPH)-induced endogenous dopamine release that led to reductions (relative to baseline) in the (11)C-raclopride-specific binding parameter (binding potential). A common assumption in bolus injection PET studies of this type is that cerebral blood flow (CBF) does not vary during the scan. The goal of this work was to examine the effect of AMPH administration on sequential PET measures of CBF. METHODS: Eight dynamic H(2)(15)O PET scans were acquired with arterial blood sampling in 6 baboons: 4 scans before AMPH (over 60 min) and 4 scans after AMPH (over 60 min) (0.6 mg/kg AMPH). Magnetic resonance images (coregistered to PET) were used to define regions of interest that included cortex, striatum (including subregions), and cerebellum. Data were analyzed using a 1-tissue compartment model. CBF was assessed through K(1) (mL/mL/min). RESULTS: Temporal patterns of the CBF alterations were similar across regions for each baboon. For 5 of 6 baboons, a general pattern of an initial increase in K(1) was observed after AMPH that gradually declined toward baseline, after minimizing anesthesia-induced variability in the in vivo measures. Although these alterations after AMPH were statistically significant in particular subcortical regions and cerebellum, such changes would not likely influence measures of (11)C-raclopride binding potential to a significant extent. CONCLUSION: These data support previous PET studies for which constant blood flow was assumed during the bolus PET (11)C-raclopride/AMPH experiment across striatal subregions, while underscoring the importance of considering effects of anesthesia when interpreting in vivo imaging parameters.     

Improvement of algorithm for quantification of regional myocardial blood flow using 15O-water with PET.

(15)O-Water and dynamic PET allow noninvasive quantification of myocardial blood flow (MBF). However, complicated image analyzing procedures are required, which may limit the practicality of this approach. We have designed a new practical algorithm, which allows stable, rapid, and automated quantification of regional MBF (rMBF) using (15)O-water PET. We designed an algorithm for setting the 3-dimensional (3D) region of interest (ROI) of the whole myocardium semiautomatically. Subsequently, a uniform input function was calculated for each subject using a time-activity curve in the 3D whole myocardial ROI. The uniform input function allows the mathematically simple and robust algorithm to estimate rMBF. METHODS: Thirty-six volunteers were used in the static (15)O-CO and dynamic (15)O-water PET studies. To evaluate the reproducibility of the estimates, a repeated (15)O-water scan was obtained under resting condition. In addition, to evaluate the stability of the new algorithm in the hyperemic state, a (15)O-water scan was obtained with adenosine triphosphate. This algorithm includes a procedure for positioning a 3D ROI of the whole myocardium from 3D images and dividing it into 16 segments. Subsequently, the uniform input function was calculated using time-activity curves in the whole myocardial ROI and in the LV ROI. The uniform input function allowed this simple and robust algorithm to estimate the rMBF, perfusable tissue fraction (PTF), and spillover fraction (Va) according to a single tissue compartment model. These estimates were compared with those calculated using the original method. A simulation study was performed to compare the effects of errors in PTF or Va on the MBF using the 2 methods. RESULTS: The average operating time for positioning a whole myocardial ROI and 16 regional myocardial ROIs was <5 min. The new method yielded less deviation in rMBF (0.876 +/- 0.177 mL/min/g, coefficient of variation [CV] = 20.2%, n = 576) than those with the traditional method (0.898 +/- 0.271 mL/min/g, CV = 30.1%, n = 576) (P < 0.01). In the hyperemic state, the new method yielded less deviation in rMBF (3.890 +/- 1.250 mL/min/g, CV = 32.1%) than those with the traditional method (3.962 +/- 1.762 mL/min/g, CV = 44.4%) (P < 0.05). This method yielded significantly higher reproducibility of rMBF (r = 0.806, n = 576) than the original method (r = 0.756, n = 576) (P < 0.05). Our new method yielded a better correlation in the repeated measurement values of rMBF and less variability among the regions in the myocardium than with the original theory of the (15)O-water technique. The simulation study demonstrated fewer effects of error in the PTF or Va on the MBF value with the new method. CONCLUSION: We have developed a technique for an automated, simplified, and stable algorithm to quantify rMBF. This software is considered to be practical for clinical use in myocardial PET studies using (15)O-water with a high reproducibility and a short processing time.     

Validation of myocardial perfusion reserve measurements using regularized factor images of H(2)(15)O dynamic PET scans.

The use of H(2)(15)O PET scans for the measurement of myocardial perfusion reserve (MPR) has been validated in both animal models and humans. Nevertheless, this protocol requires cumbersome acquisitions such as C(15)O inhalation or (18)F-FDG injection to obtain images suitable for determining myocardial regions of interest. Regularized factor analysis is an alternative method proposed to define myocardial contours directly from H(2)(15)O studies without any C(15)O or FDG scan. The study validates this method by comparing the MPR obtained by the regularized factor analysis with the coronary flow reserve (CFR) obtained by intracoronary Doppler as well as with the MPR obtained by an FDG acquisition. METHODS: Ten healthy volunteers and 10 patients with ischemic cardiopathy or idiopathic dilated cardiomyopathy were investigated. The CFR of patients was measured sonographically using a Doppler catheter tip placed into the proximal left anterior descending artery. The mean velocity was recorded at baseline and after dipyridamole administration. All subjects underwent PET imaging, including 2 H(2)(15)O myocardial perfusion studies at baseline and after dipyridamole infusion, followed by an FDG acquisition. Dynamic H(2)(15)O scans were processed by regularized factor analysis. Left ventricular cavity and anteroseptal myocardial regions of interest were drawn independently on regularized factor images and on FDG images. Myocardial blood flow (MBF) and MPR were estimated by fitting the H(2)(15)O time-activity curves with a compartmental model. RESULTS: In patients, no significant difference was observed among the 3 methods of measurement-Doppler CFR, 1.73 +/- 0.57; regularized factor analysis MPR, 1.71 +/- 0.68; FDG MPR, 1.83 +/- 0.49-using a Friedman 2-way ANOVA by ranks. MPR measured with the regularized factor images correlated significantly with CFR (y = 1.17x - 0.30; r = 0.97). In the global population, the regularized factor analysis MPR and FDG MPR correlated strongly (y = 0.99x; r = 0.93). Interoperator repeatability on regularized factor images was 0.126 mL/min/g for rest MBF, 0.38 mL/min/g for stress MBF, and 0.34 for MPR (19% of mean MPR). CONCLUSION: Regularized factor analysis provides well-defined myocardial images from H(2)(15)O dynamic scans, permitting an accurate and simple measurement of MPR. The method reduces exposure to radiation and examination time and lowers the cost of MPR protocols using a PET scanner.     

Quantification of subendocardial and subepicardial blood flow using 15O-labeled water and PET: experimental validation.

The purpose of this study was to assess the feasibility and accuracy of quantifying subendocardial and subepicardial myocardial blood flow (MBF) and the relative coronary flow reserves (CFR) using (15)O-labeled water (H(2)(15)O) and 3-dimensional-only PET. METHODS: Eight pigs were scanned with H(2)(15)O and (15)O-labeled carbon monoxide (C(15)O) after partially occluding the circumflex (n = 3) or the left anterior descending (n = 5) coronary artery, both at rest and during hyperemia induced by intravenous dipyridamole. Radioactive microspheres were injected during each of the H(2)(15)O scans. RESULTS: In a total of 256 paired measurements of MBF, ranging from 0.30 to 4.46 mL.g(-1).min(-1), microsphere and PET MBF were fairly well correlated. The mean difference between the 2 methods was -0.01 +/- 0.52 mL.g(-1).min(-1) with 95% of the differences lying between the limits of agreement of -1.02 and 1.01 mL.g(-1).min(-1). CFR was significantly reduced (P < 0.05) in the ischemic subendocardium (PET = 1.12 +/- 0.45; microspheres = 1.09 +/- 0.50; P = 0.86) and subepicardium (PET = 1.2 +/- 0.35; microspheres = 1.32 +/- 0.5; P = 0.39) in comparison with remote subendocardium (PET = 1.7 +/- 0.62; microspheres = 1.64 +/- 0.61; P = 0.68) and subepicardium (PET = 1.79 +/- 0.73; microspheres = 2.19 +/- 0.86; P = 0.06). CONCLUSION: Dynamic measurements using H(2)(15)O and a 3-dimensional-only PET tomograph allow regional estimates of the transmural distribution of MBF over a wide flow range, although transmural flow differences were underestimated because of the partial-volume effect. PET subendocardial and subepicardial CFR were in good agreement with the microsphere values.     

Reproducibility of tumor blood flow quantification with 15O-water PET

Noninvasive methods for quantifying tumor blood flow (TBF) have a potentially important role in the field of drug development. (15)O-water PET has been used in several studies aimed at monitoring response to novel treatments. Assessing the significance of changes in TBF requires knowledge of the reproducibility of the technique. This article quantifies the reproducibility of the (15)O-water technique for TBF applications. METHODS: A total of 43 pairs of replicate (15)O-water studies were performed on 23 different patients with cancer. TBF was estimated using a standard, single-compartment model, and the replicate data were used to assess the reproducibility of the method. RESULTS: The magnitude of the differences between replicate flow measurements was found to be proportional to their means. TBF was measured with a within-subject coefficient of variation of 13.4% and a repeatability of 37.1%. The volume of distribution was measured with a within-subject coefficient of variation of 8.6% and a repeatability of 24.0%. CONCLUSION: (15)O-water PET can be used to measure TBF with a reproducibility that is consistent with other applications of the technique. The short half-life of the isotope permits multiple replicate studies to be performed during the same imaging session, allowing the reproducibility of the average flow estimate to be adapted to the required task. (15)O-water PET is a powerful and robust tool for TBF quantification.     

Effect of vascular radioactivity on regional values of cerebral blood flow: evaluation of methods for H(2)(15)O PET to distinguish cerebral perfusion from blood volume.

To evaluate the appropriate model for calculating regional cerebral blood flow (rCBF) with PET and H(2)(15)O, the values obtained from 1- and 2-compartment analyses were compared. METHODS: Dynamic PET scans were performed on 12 healthy volunteers after injection of H(2)(15)O in 2 conditions of baseline and visual stimulation. Calculation of rCBF was performed using the 2-weighted integral (WI) and autoradiographic methods for the 1-compartment analysis, and the 3-WI method was followed for the 2-compartment analysis. Arterial blood radioactivity was counted continuously and corrected for delay and dispersion. The rCBF images were transformed into the Talairach space and analyzed by statistical parametric mapping to identify regional differences in the 2 methods. The values obtained from regions of interest also were compared. RESULTS: Although the difference in global CBF between the 2 models was not significant, rCBF values in the large arteries and neighbor areas were significantly greater in the 2-WI method than in the 3-WI method. However, regional differences in the activation studies were not affected when the 2 methods were compared. The images of cerebral arterial blood volume (V(0)) obtained by the 3-WI method showed a significant increase in V(0) in the visual cortex during visual stimulation. CONCLUSION: These results suggest that the rCBF values in the 1-compartment analysis were affected by radioactivity in the vessels. The 3-WI method could provide rCBF values that are less influenced by vascular radioactivity and also show differences in V(0) in PET activation studies.     

Will 3-dimensional PET-CT enable the routine quantification of myocardial blood flow?

Quantification of myocardial blood flow (MBF) and flow reserve has been used extensively with positron emission tomography (PET) to investigate the functional significance of coronary artery disease. Increasingly, flow quantification is being applied to investigations of microvascular dysfunction in early atherosclerosis and in nonatherosclerotic microvascular disease associated with primary and secondary cardiomyopathies. Fully three-dimensional (3D) acquisition is becoming the standard imaging mode on new equipment, bringing with it certain challenges for cardiac PET, but also the potential for MBF to be measured simultaneously with routine electrocardiography (ECG)-gated perfusion imaging. Existing 3D versus 2D comparative studies support the use of 3D cardiac PET for flow quantification, and these protocols can be translated to PET-CT, which offers a virtually noise-free attenuation correction. This technology combines the strengths of cardiac CT for evaluation of anatomy with cardiac PET for quantification of the hemodynamic impact on the myocardium. High throughput clinical imaging protocols are needed to evaluate the incremental diagnostic and prognostic value of this technology. An erratum to this article is available at .     

Brain blood flow measured with intravenous H2(15)O. I. Theory and error analysis

The tissue autoradiographic method for the measurement of regional cerebral blood flow (rCBF) in animals was adapted for use with positron emission tomography (PET). Because of the limited spatial resolution of PET, a region of interest will contain a mix of gray and white matter, inhomogeneous in flow and in tracer partition coefficient (lambda). The resultant error in rCBF, however, is less than 4%. Although the tissue autoradiographic method requires a monotonically increasing input function to ensure a unique solution for flow, the PET adaptation does not, because of an additional integration in the operational equation. Simulation showed that the model is accurate in the presence of ischemia or hyperemia of the gray matter. Inaccuracy in timing of the arterial input function will result in large errors in rCBF measurement. Propagation of errors in measurement of tissue activity is largely independent of flow, reflecting the nearly linear flow compared with activity relationship.     

Blind separation of cardiac components and extraction of input function from H(2)(15)O dynamic myocardial PET using independent component analysis.

The independent component analysis (ICA) method is suggested to be useful for separation of the ventricles and the myocardium and for extraction of the left ventricular input function from the dynamic H(2)(15)O myocardial PET. The ICA-generated input function was validated with the sampling method, and the myocardial blood flow (MBF) calculated with this input function was compared with the microsphere results. METHODS: We assumed that the elementary activities of the ventricular pools and the myocardium were spatially independent and that the mixture of them composed dynamic PET image frames. The independent components were estimated by recursively minimizing the mutual information (measure of dependence) between the components. The ICA-generated input functions were compared with invasively derived arterial blood samples. Moreover, the regional MBF calculated using the ICA-generated input functions and single-compartment model was correlated with the results obtained from the radiolabeled microspheres. RESULTS: The ventricles and the myocardium were successfully separated in all cases within a short computation time (<15 s). The ICA-generated input functions displayed shapes similar to those obtained by arterial sampling except that they had a smoother tail than those obtained by sampling, which meant that ICA removed the statistical noise from the time--activity curves. The ICA-generated input function showed a longer time delay of peaks than those obtained by arterial sampling. MBFs estimated using the ICA-generated input functions ranged from 1.10 to approximately 2.52 mL/min/g at rest and from 1.69 to approximately 8.00 mL/min/g after stress and correlated well with those calculated with microspheres (y = 0.45 + 0.98x; r = 0.95, P < 0.000). CONCLUSION: ICA, a rapid and reliable method for extraction of the pure physiologic components, was a valid and useful method for quantification of the regional MBF using H(2)(15)O PET.