Parametric renal blood flow imaging using [15O]H2O and PET.

PURPOSE: The quantitative assessment of renal blood flow (RBF) may help to understand the physiological basis of kidney function and allow an evaluation of pathophysiological events leading to vascular damage, such as renal arterial stenosis and chronic allograft nephropathy. The RBF may be quantified using PET with H(2)(15)O, although RBF studies that have been performed without theoretical evaluation have assumed the partition coefficient of water (p, ml/g) to be uniform over the whole region of renal tissue, and/or radioactivity from the vascular space (V(A). ml/ml) to be negligible. The aim of this study was to develop a method for calculating parametric images of RBF (K(1), k(2)) as well as V(A) without fixing the partition coefficient by the basis function method (BFM). METHODS: The feasibility was tested in healthy subjects. A simulation study was performed to evaluate error sensitivities for possible error sources. RESULTS: The experimental study showed that the quantitative accuracy of the present method was consistent with nonlinear least-squares fitting, i.e. K(1,BFM)=0.93K(1,NLF)-0.11 ml/min/g (r=0.80, p<0.001), k(2,BFM)=0.96k(2,NLF)-0.13 ml/min/g (r=0.77, p<0.001), and V(A,BFM)=0.92V(A,NLF)-0.00 ml/ml (r=0.97, p<0.001). Values of the Akaike information criterion from this fitting were the smallest for all subjects except two. The quality of parametric images obtained was acceptable. CONCLUSION: The simulation study suggested that delay and dispersion time constants should be estimated within an accuracy of 2 s. V(A) and p cannot be neglected or fixed, and reliable measurement of even relative RBF values requires that V(A) is fitted. This study showed the feasibility of measurement of RBF using PET with H(2)(15)O.

Functional Pulmonary Magnetic Resonance Imaging for Detection of Ischemic Injury in a Porcine Ex-Vivo Lung Perfusion System Prior to Transplantation.

RATIONALE AND OBJECTIVES: To evaluate the feasibility of multiparametric magnetic resonance imaging (MRI) of the lungs to detect impaired organ function in a porcine model of ischemic injury within an ex-vivo lung perfusion system (EVLP) prior to transplantation. MATERIALS AND METHODS: Twelve pigs were anesthetized, and left lungs were clamped to induce warm ischemia for 3 hours. Right lungs remained perfused as controls. Lungs were removed and installed in an EVLP for 12 hours. Lungs in the EVLP were imaged repeatedly using computed tomography, proton MRI (1H-MRI) and fluorine MRI (19F-MRI). Dynamic contrast-enhanced derived parenchymal blood volume, oxygen washout times, and 19F washout times were calculated. PaO2 was measured for ischemic and normal lungs, wet/dry ratio was determined, histologic samples were assessed, and cytokines in the lung tissue were analyzed. Statistical analysis was performed using nonparametric testing. RESULTS: Eleven pigs were included in the final analysis. Ischemic lungs showed significantly higher wet/dry ratios (p = 0.024), as well as IL-8 tissue levels (p = 0.0098). Histologic assessment as well as morphologic scoring of computed tomography and 1H-MRI did not reveal significant differences between ischemic and control lungs. 19F washout (p = 0.966) and parenchymal blood flow (p = 0.32) were not significantly different. Oxygen washout was significantly prolonged in ischemic lungs compared to normal control lungs at the beginning (p = 0.018) and further prolonged at the end of the EVLP run (p = 0.005). CONCLUSION: Multiparametric pulmonary MRI is feasible in lung allografts within an EVLP system. Oxygen-enhanced imaging seems to be a promising marker for ischemic injury, enabling detection of affected lung segments prior to transplantation.

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

UNLABELLED: 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.

Real-time iterative monitoring of radiofrequency ablation tumor therapy with 15O-water PET imaging.

UNLABELLED: A method that provides real-time image-based monitoring of solid tumor therapy to ensure complete tumor eradication during image-guided interventional therapy would be a valuable tool. The short, 2-min half-life of (15)O makes it possible to perform repeated PET imaging at 20-min intervals at multiple time points before and after image-guided therapy. In this study, (15)O-water PET was evaluated as a tool to provide real-time feedback and iterative image guidance to rapidly monitor the intratumoral coverage of radiofrequency (RF) ablation therapy. METHODS: Tumor RF ablation therapy was performed on head and neck squamous cell carcinoma (SCC) xenograft tumors (length, approximately 23 mm) in 6 nude rats. The tumor in each animal was ablated with RF (1-cm active size ablation catheter, 70 degrees C for 5 min) twice in 2 separate tumor regions with a 20-min separation. The (15)O-water PET images were acquired before RF ablation and after the first RF and second RF ablations using a small-animal PET scanner. In each PET session, approximately 100 MBq of (15)O-water in 1.0 mL of saline were injected intravenously into each animal. List-mode PET images were acquired for 7 min starting 20 s before injection. PET images were reconstructed by 2-dimensional ordered-subset expectation maximization into single-frame images and dynamic images at 10 s/frame. PET images were displayed and analyzed with software. RESULTS: Pre-RF ablation images demonstrate that (15)O-water accumulates in tumors with (15)O activity reaching peak levels immediately after administration. After RF ablation, the ablated region had almost zero activity, whereas the unablated tumor tissue continued to have a high (15)O-water accumulation. Using image feedback, the RF probe was repositioned to a tumor region with residual (15)O-water uptake and then ablated. The second RF ablation in this new region of the tumor resulted in additional ablation of the solid tumor, with a corresponding decrease in activity on the (15)O-water PET image. CONCLUSION: (15)O-water PET clearly demonstrated the ablated tumor region, whereas the unablated tumor continued to show high (15)O-water accumulation. (15)O-water imaging shows promise as a tool for on-site, real-time monitoring of image-guided interventional cancer therapy.

Cell killing, nuclear damage and apoptosis in Chinese hamster V79 cells after irradiation with heavy-ion beams of (16)O, (12)C and (7)Li.

Chinese hamster V79 cells were exposed to high LET (linear energy transfer) (16)O-beam (625keV/mum) radiation in the dose range of 0-9.83Gy. Cell survival, micronuclei (MN), chromosomal aberrations (CA) and induction of apoptosis were studied as a follow up of our earlier study on high LET radiations ((7)Li-beam of 60keV/mum and (12)C-beam of 295keV/mum) as well as (60)Co gamma-rays. Dose dependent decline in surviving fraction was noticed along with the increase of MN frequency, CA frequency as well as percentage of apoptosis as detected by nuclear fragmentation assay. The relative intensity of DNA ladder, which is a useful marker for the determination of the extent of apoptosis induction, was also increased in a dose dependent manner. Additionally, expression of tyrosine kinase lck-1 gene, which plays an important role in response to ionizing radiation induced apoptosis, was increased with the increase of radiation doses and also with incubation time. The present study showed that all the high LET radiations were generally more effective in cell killing and inflicting other cytogenetic damages than that of low LET gamma-rays. The dose response curves revealed that (7)Li-beam was most effective in cell killing as well as inducing other nuclear damages followed by (12)C, (16)O and (60)Co gamma-rays, in that order. The result of this study may have some application in biological dosimetry for assessment of genotoxicity in heavy ion exposed subjects and in determining suitable doses for radiotherapy in cancer patients where various species of heavy ions are now being generally used.

Estimation of oxygen metabolism in a rat model of permanent ischemia using positron emission tomography with injectable15O-O2.

The threshold of cerebral blood flow (CBF) into infarction in rats has been indicated to be similar to that in patients. However, CBF does not reflect metabolic function, and so estimations of oxygen metabolism have been required. Here, we estimated changes in oxygen metabolism after occluding the right middle cerebral artery (MCA) in rats using an injectable (15)O-O(2) we developed. A decrease in CBF (left: 0.67+/-0.22 mL/min/g, right: 0.44+/-0.17 mL/min/g, P<0.05) and compensatory increase in the oxygen extraction fraction (OEF) (left: 0.42+/-0.13, right: 0.50+/-0.19, P<0.05) were observed at 1-h after occlusion. In contrast, a marked decrease in CBF and the cerebral metabolic rate for oxygen and a collapse of the compensatory OEF mechanism were found at 24 h after occlusion. Injectable (15)O-O(2) could be used to reliably estimate oxygen metabolism in an infarction rat model with positron emission tomography.