Parametric images of blood flow in oncology PET studies using [15O]water.

PET was used to measure tumor blood flow, which is potentially valuable for diagnosis and assessing the effects of therapy. To help visualize regional differences in blood flow and to improve the accuracy of region-of-interest placement, a parametric imaging approach was developed and compared with the standard region-of-interest method. METHODS: Five patients with renal cell metastases in the thorax were studied using [15O]water and dynamic PET. To assess the reproducibility of the blood flow measurements, multiple water studies were performed on each patient. Model fitting was done on a pixel-by-pixel basis using several different formulations of the standard single-compartment model. RESULTS: The tumors studied spanned a wide range of blood flows, varying from 0.4 to 4.2 mL/min/g. These values were generally high compared with those of most other tissues, which meant that the tumors could be readily identified in parametric images of flow. The different model formulations produced images with different characteristics, and no model was entirely valid throughout the field of view. Although tumor blood flow measured from the parametric images was largely unbiased with respect to a standard regional method, large errors were observed with certain models in regions of low flow. The most robust model throughout the field of view had only 1 free parameter and, compared with a regional method, gave rise to a flow bias of 0.3%+/-3.1% for tumor and 16%+/-11% for low-flow soft tissue (muscle plus fat). With this model, tumor blood flow was measured with an SD of 7.6%+/-4.0%. CONCLUSION: Parametric imaging provides a convenient way of visualizing regional changes in blood flow, which may be valuable in studies of tumor blood flow.     

Imaging of blood flow and hypoxia in head and neck cancer: initial evaluation with [(15)O]H(2)O and [(18)F]fluoroerythronitroimidazole PET.

Hypoxia is a characteristic feature of malignant tumors that should be evaluated before the start of therapy. (18)F-labeled fluoroerythronitroimidazole (FETNIM) is a possible candidate for imaging tumor hypoxia with PET. Quantitative analysis of [(18)F]FETNIM uptake in vivo is necessary before proceeding to assays predicting hypoxia. METHODS: Eight patients with untreated head and neck squamous cell carcinoma were enrolled in the study. All patients underwent dynamic PET imaging with [(18)F]FETNIM, coupled with measurements of blood flow with [(15)O]H(2)O and blood volume with [(15)O]CO. The metabolically active tumor volume was determined from [(18)F]FDG PET performed on a separate day. [(18)F]FETNIM uptake in the tumor was correlated with that in neck muscles and arterial plasma and compared with the findings of other PET studies. RESULTS: Blood flow in tumor was 5- to 30-fold greater than in muscle, in contrast to blood volume, which did not significantly differ in the 2 tissues. With [(18)F]FETNIM PET, muscle activity remained invariably less than plasma activity, whereas activity in whole tumors was always greater than that in muscle. In 4 instances, the maximum tumor uptake of [(18)F]FETNIM was 1.2-2.0 times higher than plasma activity in the late dynamic phase. A kinetic model developed for calculation of distribution volume of reversibly trapping tracers was successfully applied in the [(18)F]FETNIM studies. Tumor distribution volume correlated strongly with the standardized uptake value of [(18)F]FETNIM between 60 and 120 min and with blood flow but not with the standardized uptake value of [(18)F]FDG. The relationship between [(18)F]FETNIM uptake and the blood flow of the tumor was less obvious on a pixel-by-pixel level. CONCLUSION: Uptake of [(18)F]FETNIM in head and neck cancer is highly variable and seems to be governed by blood flow at least in the early phase of tissue accumulation. Maximum tumor-to-muscle tracer uptake ratios > 180 min were in the range of 1-4, comparing favorably with those reported previously for [(18)F]fluoromisonidazole. Assessment of the distribution volume of [(18)F]FETNIM after the initial blood-flow phase is feasible for subsequent evaluation of hypoxia-specific retention.     

Synthesis, biodistribution and micro-PET imaging of a potential cancer biomarker carbon-11 labeled MMP inhibitor (2R)-2-[[4-(6-fluorohex-1-ynyl)phenyl]sulfonylamino]-3-methylbutyric acid [11C]methyl ester

(2R)-2-[[4-(6-fluorohex-1-ynyl)phenyl]sulfonylamino]-3-methylbutyric acid [(11)C]methyl ester ([(11)C]FMAME), a novel carbon-11 labeled matrix metalloproteinase (MMP) inhibitor, has been synthesized for evaluation as new potential positron emission tomography (PET) cancer biomarker. [(11)C]FMAME was prepared by appropriate precursor (2R)-2-[[4-(6-fluorohex-1-ynyl)phenyl]sulfonylamino]-3-methylbutyric acid (FMA), which was synthesized in six steps from (D)-valine in 71% chemical yield. This acid precursor was labeled by [(11)C]methyl triflate through O-[(11)C]methylation method under basic conditions and isolated by solid-phase extraction (SPE) purification to produce pure target compound in 40-55% radiochemical yield, based on (11)CO(2), decay corrected to end of bombardment, and 15-20 min synthesis time. The biodistribution of [(11)C]FMAME was determined at 30 min post IV injection in breast cancer animal models MCF-7 transfected with IL-1 alpha implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptakes of [(11)C]FMAME in these tumors were 1.13% dose/g in MCF-7 transfected with IL-1 alpha implanted mice and 1.37% dose/g in MDA-MB-435 implanted mice, respectively; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.05 +/- 0.29 (T/M, MCF-7's), 0.77 +/- 0.20 (T/B, MCF-7's) and 0.99 +/- 0.35 (T/M, MDA-MB-435), 1.44 +/- 0.69 (T/B, MDA-MB-435), respectively. Pretreatment of MCF-7 transfected with IL-1 alpha tumor-bearing mice with MMP inhibitor FMA had no effect on [(11)C]FMAME biodistribution. Likewise, pretreatment of MDA-MB-435 tumor-bearing mice with FMA also showed no effect on [(11)C]FMAME biodistribution. The micro-PET images were acquired for 15 min from a MCF-7 transfected with IL-1 alpha tumor-bearing mouse or a MDA-MB-435 tumor-bearing mouse at 30 min post IV injection of 1 mCi of [(11)C]FMAME using a dedicated high resolution (<3 mm full-width at half-maximum) PET imaging system (Indy-PET II scanner). The initial dynamic micro-PET images of [(11)C]FMAME in a MCF-7 transfected with IL-1 alpha tumor-bearing mouse during different time periods of 0-15, 15-30, 30-45 and 45-60 min were performed by Indy-PET II. The PET images clearly showed both tumors were visible with [(11)C]FMAME. These results suggest that the localization of [(11)C]FMAME in the tumor is mediated by non-specific processes, and the visualization of [(11)C]FMAME on the tumor using the Indy-PET II scanner is related to non-specific binding.     

Alginate moulding: an empirical method for magnetic resonance imaging/positron emission tomography co-registration in a tumor rat model

BACKGROUND AND PURPOSE: In the experimental field of animal models, co-registration between positron emission tomography (PET) and magnetic resonance imaging (MRI) data still relies on non-automated post-processing using sophisticated algorithms and software developments. We assessed the value of an empirical method using alginate moulding for PET-MR co-registration in a tumor rat model. METHODS: Male WAG/RijHsd rats bearing grafted syngenic rhabdomyosarcoma were examined under general anesthesia by MRI using a clinical whole-body 3-T system equipped with a sensitivity-encoding four-channel wrist coil and by a small animal PET system using labelled [(18)F]-fluorocholine as tracer. An alginate mould including a system of external fiducials was manufactured for each animal, allowing strict immobilization and similar positioning for both modalities. Fourteen rats (27 tumors) had only one MR/PET imaging session. Five rats (9 tumors) had a similar MR/PET session before and 3 days after external radiation therapy (13 Gy in one fraction) using the same mould. Co-registration was performed using the Pmod release 2.75 software (PMOD Technologies, Ltd., Adliswil, Switzerland) with mutual information algorithm. RESULTS: The manufacture of the alginate moulds was easy and innocuous. Imaging sessions were well tolerated. PET-MR co-registration based on mutual information was perfect at visual examination, which was confirmed by the superimposition of external fiducials on fused images. Reuse of the same mould for the post-therapeutic session was feasible 3 days after the pre-therapeutic one in spite of tumor growth. CONCLUSION: The empirical method using alginate moulding with external fiducials for PET-MR co-registration in a rodent tumor model was feasible and accurate.     

Positron Emission Tomography (PET) with 1-Aminocyclobutane-1-[(11)C]carboxylic Acid (1-[(11)C]-ACBC) for Detecting Recurrent Brain Tumors

This study was done to determine whether 1-[(11)C]ACBC PET has any advantages over 2-[(18)F]FDG PET, CT, or MRI in detecting recurrent brain tumors, and whether quantitative 1-[(11)C]ACBC PET information improves the accuracy of "visual" image interpretation.Twenty patients with recurrent brain tumor underwent dynamic PET. Images were analyzed by visual interpretation; in addition, standardized uptake values (SUVs) and Patlak values (k(1)*k(3)/k) were evaluated.1-[(11)C]ACBC identified 19/20 recurrent brain tumors, [18F]FDG 13/19, MRI 13/19, and CT 8/16. Based on SUVs, the average tumor-to-contralateral gray matter ratio of 1-[(11)C]ACBC was 5.0 and 0.5 for 2-[(18)F]FDG. Mean Patlak values of 1-[(11)C]ACBC were 0.044 +/- 0.047 for high and 0.034 +/- 0.026 for low grade tumors. However, visual interpretation was effective without quantitative PET data.1-[(11)C]ACBC, accurately detects recurrent tumors for selecting biopsy sites and treatment planning.     

Tumor volume in pharyngolaryngeal squamous cell carcinoma: comparison at CT, MR imaging, and FDG PET and validation with surgical specimen

PURPOSE: To compare computed tomography (CT), magnetic resonance (MR) imaging, and fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for delineation of gross tumor volume (GTV) in pharyngolaryngeal squamous cell carcinoma and to validate results with the macroscopic surgical specimen when available. MATERIALS AND METHODS: Twenty-nine patients with stages II-IV squamous cell carcinoma treated with radiation therapy or chemotherapy and radiation therapy (n = 20) or with total laryngectomy (n = 9) were enrolled. Ten patients had oropharyngeal, 13 had laryngeal, and six had hypopharyngeal tumors. CT, MR imaging, and PET were performed with patients immobilized in a customized thermoplastic mask, and images were coregistered. GTVs obtained with the three modalities were compared quantitatively and qualitatively. If patients underwent total laryngectomy, images were validated with the surgical specimen after three-dimensional coregistration. The effect of each modality was estimated with linear mixed-effects models. Adjustments for multiple comparisons were made with the Bonferonni or Sidak method. RESULTS: For oropharyngeal tumors and for laryngeal or hypopharyngeal tumors, no significant difference (P >.99) was observed between average GTVs delineated at CT (32.0 and 21.4 cm(3), respectively) or MR imaging (27.9 and 21.4 cm(3), respectively), whereas average GTVs at PET were smaller (20.3 [P 相似文献   

Gluc-Lys([18F]FP)-TOCA PET in patients with SSTR-positive tumors: biodistribution and diagnostic evaluation compared with [111In]DTPA-octreotide.

A recently developed (18)F-labeled PET tracer for somatostatin receptor (sstr) imaging, N(alpha)-(1-deoxy-D-fructosyl)-N(epsilon)-(2-[(18)F]fluoropropionyl)-Lys(0)-Tyr(3)-octreotate (Gluc-Lys([(18)F]FP)-TOCA), was evaluated in patients with sstr-positive tumors by assessing the pharmacokinetics, biodistribution, and diagnostic performance in comparison with [(111)In]DTPA-octreotide. METHODS: Twenty-five patients with different sstr-positive tumors were included in the study and were injected with 105 +/- 50 MBq Gluc-Lys([(18)F]FP)-TOCA. PET was performed up to 120 min with 2 different dynamic imaging protocols. Tracer kinetics in tumors and nontumor tissues and tumor-to-background ratios were described by region-of-interest analysis and standardized uptake values (SUVs). In 16 patients, sstr scintigraphy with [(111)In]DTPA-octreotide was performed (whole-body scans and SPECT). Two independent experts on PET and gamma- camera scans performed lesion counts. RESULTS: Gluc-Lys([(18)F]FP)-TOCA showed a fast and intense tumor accumulation as well as a rapid clearance from blood serum (biexponential elimination, with the half-lives of the initial and the terminal elimination phase calculated as t(1/2)(1) = 2.3 +/- 1.3 min and t(1/2)(2) = 26.4 +/- 14.6 min, respectively). Tumor-to-background ratios at 16 +/- 9 min and 34 +/- 12 min were as high as 80% and 90% (% of maximum ratios), respectively. Tumors showed high SUVs ranging from 13.7 +/- 2.3 (tumors in lung) up to 26.9 +/- 15.4 (abdominal tumors). Tracer distribution within tumor and nontumor tissues was stable up to 120 min (except spleen). No significant bowel activity was observed. Comparison of 29 tumors located in the liver showed a mean tumor-to-background ratio of 5.3 +/- 2.6 for Gluc-Lys([(18)F]FP)-TOCA vs. 4.6 +/- 3.3 for [(111)In]DTPA-octreotide (P = 0.24). Visual image analysis revealed a significantly higher number of lesions (factor of 2.4) and improved interobserver correlation (r = 0.99 vs. 0.86) for PET. CONCLUSION: Gluc-Lys([(18)F]FP)-TOCA PET allows a fast, high- contrast imaging of sstr-positive tumors. The biokinetics and diagnostic performance of Gluc-Lys([(18)F]FP)-TOCA are superior to [(111)In]DTPA-octreotide and-as far as can be derived from the literature-comparable with [(68)Ga]-DOTA-d Phe(1)-Tyr(3)-octreotide ([(68)Ga]DOTATOC).     

Estimation of myocardial blood flow and myocardial flow reserve by <Superscript>99m</Superscript>Tc-sestamibi imaging: comparison with the results of [<Superscript>15</Superscript>O]H<Subscript>2</Subscript>O PET

We developed a noninvasive method to quantitatively estimate the myocardial blood flow (MBF) index and flow reserve (MFR) using dynamic and static data obtained with technetium-99m sestamibi, and compared the results with MBF and MFR measured by oxygen-15-labeled water ([(15)O]H(2)O) PET. Twenty patients with coronary artery disease (CAD) and nine normal subjects underwent both (99m)Tc-sestamibi and PET studies within 2 weeks. From the anterior view, dynamic data were acquired for 2 min immediately after the injection of (99m)Tc-sestamibi, and planar static images were also obtained after 5 min at rest and during ATP stress (0.16 mg kg(-1) min(-1) for 5 min) on another day. The area under the time-activity curve on the aortic arch (Aorta ACU), myocardial weight with the SPET image (M), and the myocardial count on the planar image for 1 min (C(m)) were obtained. The MBF index (MBFI) was calculated as follows: MBFI=Cm/Aorta ACU x 100M. MFR was measured by dividing the MBFI at ATP stress by MBFI at rest. The MBFI measured by (99m)Tc-sestamibi was significantly correlated with MBF obtained using [(15)O]H(2)O PET (MBFI=13.174+11.732 x MBF, r=0.821, P<0.001). Furthermore, MFR measured by (99m)Tc-sestamibi was well correlated with that obtained using [(15)O]H(2)O PET, with some underestimation (r=0.845, P<0.001). MFR using (99m)Tc-sestamibi in patients with CAD was significantly lower than that in normal subjects (CAD: 1.484+/-0.256 vs normal: 2.127+/-0.308, P<0.001). These data suggest that the MBFI and MFR can be measured with (99m)Tc-sestamibi. This may be useful for the quantitative assessment of CAD, especially in those patients with diffuse coronary disease.     

Evaluation of F-18-labeled amino acid derivatives and [18F]FDG as PET probes in a brain tumor-bearing animal model

2-Deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) has been extensively used as positron emission tomography (PET) tracer in clinical tumor imaging. This study compared the pharmacokinetics of two (18)F-labeled amino acid derivatives, O-2-[(18)F]fluoroethyl-l-tyrosine (l-[(18)F]FET) and 4-borono-2-[(18)F]fluoro-l-phenylalanine-fructose (l-[(18)F]FBPA-Fr), to that of [(18)F]FDG in an animal brain tumor model. METHODS: A self-modified automated PET tracer synthesizer was used to produce no-carrier-added (nca) l-[(18)F]FET. The cellular uptake, biodistribution, autoradiography and microPET imaging of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG were performed with F98 glioma cell culture and F98 glioma-bearing Fischer344 rats. RESULTS: The radiochemical purity of l-[(18)F]FET was >98% and the radiochemical yield was 50% in average of 16 runs. The uptake of l-[(18)F]FET and l-[(18)F]FBPA-Fr in the F98 glioma cells increased rapidly for the first 5 min and reached a steady-state level after 10 min of incubation, whereas the cellular uptake of [(18)F]FDG kept increasing during the study period. The biodistribution of l-[(18)F]FET, l-[(18)F]FBPA-Fr and [(18)F]FDG in the brain tumors was 1.26+/-0.22, 0.86+/-0.08 and 2.77+/-0.44 %ID/g at 60 min postinjection, respectively, while the tumor-to-normal brain ratios of l-[(18)F]FET (3.15) and l-[(18)F]FBPA-Fr (3.44) were higher than that of [(18)F]FDG (1.44). Both microPET images and autoradiograms of l-[(18)F]FET and l-[(18)F]FBPA-Fr exhibited remarkable uptake with high contrast in the brain tumor, whereas [(18)F]FDG showed high uptake in the normal brain and gave blurred brain tumor images. CONCLUSION: Both l-[(18)F]FET and l-[(18)F]FBPA-Fr are superior to [(18)F]FDG for the brain tumor imaging as shown in this study with microPET.     

Comparison of transcatheter intraarterial perfusion MR imaging and fluorescent microsphere perfusion measurements during transcatheter arterial embolization of rabbit liver tumors

PURPOSE: Transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging is clinically used in the interventional MR imaging setting to verify distribution of injected embolic or chemoembolic material during liver-directed transcatheter therapies and to monitor reductions in perfusion. The accuracy of this technique remains unknown. In the present study, rabbit VX2 liver tumors were used to test the hypothesis that TRIP MR imaging accurately measures changes in tumor perfusion during transcatheter arterial embolization (TAE), with injection of fluorescent microspheres used as the gold-standard technique. MATERIALS AND METHODS: Five New Zealand White rabbits were used for this study (two donor rabbits and three with VX2 liver tumors). In three rabbits with implanted VX2 liver tumors, catheters were superselectively placed under digital subtraction angiographic guidance into the left hepatic artery supplying the targeted tumor. Fluorescent microspheres were injected into each rabbit's left ventricle before and after TAE. TRIP MR images were obtained at baseline and after embolizations for all rabbits with intraarterial injections of 2.5% gadopentetate dimeglumine solution. Linear regression was used to compare relative reductions in tumor perfusion between TRIP MR imaging and fluorescent microspheres. Results were considered statistically significant at a P value less than .05. RESULTS: There was good correlation between TRIP MR imaging and fluorescent microsphere measurements of reduction in tumor perfusion (r = 0.722, P < .012). CONCLUSIONS: TRIP MR imaging provides accurate semiquantitative measurement of perfusion reduction during TAE in rabbit liver tumors.     

Characteristics of ultrasmall superparamagnetic iron oxides in patients with brain tumors

OBJECTIVE: The aim of this study was to evaluate the characteristics of an ultrasmall superparamagnetic iron oxides (USPIO) agent in patients with brain tumors and to correlate changes on MRI with histopathologic data collected systematically in all patients. SUBJECTS AND METHODS: Nine patients with brain tumors were imaged before and 24 hr after administration of a USPIO at a dose of 2.6 mg Fe/kg. Analysis of MR images included qualitative and quantitative comparison of the USPIO and gadolinium enhancement of brain tumors. Brain surgery was performed 25-112 hr after administration of the USPIO. The histopathologic workup included iron histochemistry with diaminobenzidine (DAB)-enhanced Perls stain. RESULTS: In seven of nine patients, USPIO-related changes of signal intensity were observed in gadolinium-enhancing brain tumors on T1- and T2*-weighted sequences. The difference in signal intensity on T1-weighted USPIO series was 40.1% +/- 26.7% (mean +/- SD). On T2*-weighted USPIO series, the difference in signal intensity was -33.1% +/- 18.4% in solid tumor parts. Areas of suspected radiation necrosis did not enhance in three patients with prior radiation therapy. Iron histochemistry revealed the presence of iron deposits in macrophages in two patients. CONCLUSION: USPIO agents will not replace gadolinium in the workup of patients with brain tumors. Our findings suggest that USPIO agents seem to offer complementary information and may help to differentiate between brain tumors and areas of radiation necrosis. Signal intensity changes on T2*-weighted images might be related to the blood pool properties of the agent, possibly reflecting steady-state susceptibility effects.     

Increased Metabolic Activity in the Spinal Cord of Patients with Long-Standing Lhermitte’s Sign

PURPOSE: To investigate the pathophysiology of the radiation-induced, chronic Lhermitte's sign (LS) on the basis of long-standing case histories with partial functional recovery. PATIENTS AND METHODS: As radiotherapy in two nasopharyngeal cancer patients, a biologically effective dose (BED) of 103.8 Gy(2) (case 1) and 94.8 Gy(2) (case 2) was delivered to the cervical spinal cord. Neurologic signs relating to the irradiated spinal cord segments developed after 2 months (case 1) and 5 years (case 2), with radiation-induced damage equivalent to grade 3 (case 1) and grade 2 (case 2) toxicity (Common Toxicity Criteria, Version 2.0). The clinical status improved to grade 2 (case 1) and grade 1 (case 2). Positron emission tomography (PET) and fibroblast clonogen assay were applied 25 and 7 years postirradiation, respectively, to characterize this rare clinical picture. RESULTS: PET demonstrated increased [(18)F]fluorodeoxyglucose (FDG) accumulation and [(15)O]butanol perfusion, but negligible [(11)C]methionine uptake in the irradiated spinal cord segments in both patients. In clonogenic assays, fibroblasts from case 1 displayed much higher radiation sensitivity than in healthy controls, while in case 2 the fibroblasts sensitivity was normal. CONCLUSIONS: These data suggests a close direct relationship between regional perfusion and metabolism of the spinal cord, similarly as in the brain. The postirradiation recovery may be related to energy-demanding conduction, explaining the increased metabolism and perfusion. The increased radiosensitivity and higher spinal cord BED may have contributed to the more severe sequelae in case 1.     

PET-fluorodeoxyglucose of cranial and spinal neuromas.

Five patients with eighth nerve, one with ninth nerve and one with cervical neuromas were studied with PET and [18F] fluorodeoxyglucose (FDG). Four of the patients had had surgery prior to the PET study, and six patients had subsequent surgery. All tumors were well-visualized on the PET images. Only one patient with bilateral acoustic neuroma exhibited tumor recurrence or growth after the PET study; these two lesions showed the highest FDG uptakes in the PET studies (tumor-to-cerebellum ratio of 0.93-0.98). All other tumors were relatively hypometabolic (tumor-cerebellum ratios of 0.43-0.65) and showed no tumor growth or recurrence during follow-up periods ranging from 5 to 8 yr. These results suggest that PET-FDG may be of value in the evaluation of cranial and spinal schwannomas.     

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.     

21. Increased FDG uptake in Childhood CNS Tumors is Associated with Tumor Malignancy

Background: In adults PET scanning of CNS tumors with the tracer FDG (18F-flourodeoxyglucose) can provide information about the degree of malignancy, tumor extent, and dissemination. FDG PET can also be able to assess tumor response to therapy and to differentiate recurrence from necrosis. Although CNS tumors are the most common solid tumor in childhood, so far only few PET-studies have been reported. Pre-operative assessment of malignancy would facilitate surgical planning and the use of pre-operative chemotherapy.Materials and Methods: 21 children with CNS tumors were referred to clinical FDG PET prior to therapy (M/F = 12/9, median age: 9 (range 0-16)), (4 PNET/medulloblastomas; 1 gr. III ependymoma, 16 benign tumors)). Image processing included co-registration with MRI and image fusion. The FDG uptake in the tumors was ranked 0-5 by a hotspot/cortex-ratio by two observers independently. The FDG uptake in grey and white matter was used as reference for the grading system with FDG uptakes defined as 4 and 2 respectively.Results: 15 of 16 patients with tumors WHO gr. I-II had FDG-uptake of 1-2, and all 5 patients with tumors WHO gr. III-IV had FDG-uptake of 3-4. A WHO gr. I papilloma, known to have a high metabolism caused by high mitochondrial activity, had FDG uptake of 5. Except for this tumor, the FDG uptake was positively correlated with tumor malignancy. MRI/PET co-registration and image fusion increased the specificity of tumor location, as well as of tumor extent, and of heterogeneity (e.g., areas of necrosis).Conclusion: FDG PET with MRI/PET co-registration and image fusion could be an important adjunct in the diagnostic work up of pediatric CNS tumors, and could help define patients eligible for pre-operative chemotherapy.     

Assessment of tumor oxygenation in human cervical carcinoma by use of dynamic Gd-DTPA-enhanced MR imaging.

Increased knowledge of the physiological basis behind the signal enhancement in tumors during dynamic contrast-enhanced magnetic resonance (MR) imaging may be useful in development of predictive assays based on this technique. In the present work, the relative signal intensity (RSI) increase in gadopentetate dimeglumine (Gd-DTPA)-enhanced MR images of patients with cervical carcinoma was related to tumor perfusion, vascular density, cell density, and oxygen tension (pO(2)). The patients were subjected to MR imaging before the start of treatment (N = 12) and after two weeks of radiotherapy (N = 8). Perfusion was determined from the kinetics of contrast agent in tumors and arteries, vascular density and cell density were determined from tumor biopsies, and pO(2) was determined by polarographic needle electrodes. The maximal RSI was correlated to perfusion (P = 0.002) and cell density (P = 0.004), but was not related to vascular density. There was also a correlation between pO(2) and perfusion (P < 0.001). Moreover, pO(2) tended to be correlated to cell density (P = 0.1), but was not related to vascular density. There was a significant correlation between RSI and pO(2), regardless of whether the median pO(2) (P < 0.001) or the fraction of pO(2) readings below 2.5 mmHg (P < 0.001), 5 mmHg (P < 0.0001), or 10 mmHg (P < 0.001) was considered. Our results suggest that the Gd-DTPA-induced signal enhancement in MR images of cervical tumors is influenced by both perfusion and cell density. These parameters are also of major importance for tumor oxygenation, leading to a correlation between signal enhancement and oxygenation. Dynamic contrast-enhanced MR imaging may therefore possibly be useful in prediction of treatment outcome.     

PET imaging of human cardiac opioid receptors

The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image micro and delta opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65+/-8 years old) underwent PET scanning of the chest with [(11)C]carfentanil ([(11)C]CFN) and [(11)C]- N-methyl-naltrindole ([(11)C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [(11)C]CFN or [(11)C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [(11)C]CFN and [(11)C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37+/-0.91 with [(11)C]CFN and 3.86+/-0.60 with [(11)C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [(11)C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [(11)C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function.     

Reproducibility of tumor perfusion measurements using 15O-labeled water and PET

PET and 15O-labeled water (H215O) can be used to noninvasively monitor tumor perfusion. This allows evaluation of the direct target of antiangiogenic drugs, that is, tumor vasculature. Because these drugs often result in consolidation rather than regression of the tumor mass, a change in perfusion might be a more sensitive way to evaluate response than are indirect size measures on a CT scan. However, to use the technique for serial imaging of individual patients, good reproducibility is essential. The purpose of the present study was to evaluate the reproducibility of quantitative H215O measurements. METHODS: Nine patients with non-small-cell lung cancer (NSCLC) were scanned twice within 7 d and before any therapy. All H215O scans were followed by an 18F-fluorothymidine scan to allow for adequate volume-of-interest (VOI) definition. VOIs were defined using a 3-dimensional threshold technique. Tumor perfusion and the volume of distribution (VT) were obtained using a 1-tissue-compartment model including an arterial blood volume component and an image-derived input function. The level of agreement between test and retest values was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analyses. Possible dependency on absolute values and lesion size was assessed by linear regression. RESULTS: All primary tumors and more than 90% of clinically suspected locoregional metastases could be delineated. In total, 14 lesions in 9 patients were analyzed. Tumor perfusion showed excellent reproducibility, with an ICC of 0.95 and SD of 9%. The VT was only moderately reproducible, with an ICC of 0.52 and SD of 16%. No dependency was found on absolute values of perfusion (P = 0.14) and VT (P = 0.15). In addition, tumor volume did not influence the reproducibility of perfusion (P = 0.46) and VT (P = 0.25). CONCLUSION: Quantitative measurements of tumor perfusion using H215O and PET are reproducible in NSCLC. When patients are repeatedly being scanned during therapy, changes of more than 18% in tumor perfusion and 32% in VT (>1.96 x SD) are likely to represent treatment effects.     

脑肿瘤磁敏感对比MR灌注成像技术方法的研究

研究动态敏感对比MR灌注技术在脑肿瘤研究中的应用技术和某些限制。材料和方法 :使用GEsigna1.5TMR扫描仪对本院20例头颈部疾病患者(未见颅内病变而需增强扫描者)及30例脑肿瘤患者(均经术后病理证实)进行常规平扫加增强MR检查同时使用SEEPI和GEEPI序列进行快速团注造影剂后MR灌注扫描。获得资料经在线工作站后处理分析。结果 :所有病例均获得相应功能图像及信号时间曲线 ,经肘正中静脉注射者45例均获得较为理想的功能图像及时间信号曲线。其余5例经腕表浅静脉及股静脉注射者曲线不完整。1例冠状位成像者图像变形。脂肪抑制预扫描及TR=1800ms ,TE=40ms ,FLIP角=60°的GEEPI序列为脑肿瘤灌注研究较为理想的选择。结论 :正确应用动态敏感对比MR灌注技术对脑部疾病进行定性及半定量研究 ,基本可以满足临床工作的需要