Development of a pixelated GSO gamma camera system with tungsten parallel hole collimator for single photon imaging.

PURPOSE: In small animal imaging using a single photon emitting radionuclide, a high resolution gamma camera is required. Recently, position sensitive photomultiplier tubes (PSPMTs) with high quantum efficiency have been developed. By combining these with nonhygroscopic scintillators with a relatively low light output, a high resolution gamma camera can become useful for low energy gamma photons. Therefore, the authors developed a gamma camera by combining a pixelated Ce-doped Gd(2)SiO(5) (GSO) block with a high quantum efficiency PSPMT. METHODS: GSO was selected for the scintillator, because it is not hygroscopic and does not contain any natural radioactivity. An array of 1.9 mm × 1.9 mm × 7 mm individual GSO crystal elements was constructed. These GSOs were combined with a 0.1-mm thick reflector to form a 22 × 22 matrix and optically coupled to a high quantum efficiency PSPMT (H8500C-100 MOD8). The GSO gamma camera was encased in a tungsten gamma-ray shield with tungsten pixelated parallel hole collimator, and the basic performance was measured for Co-57 gamma photons (122 keV). RESULTS: In a two-dimensional position histogram, all pixels were clearly resolved. The energy resolution was ∼15% FWHM. With the 20-mm thick tungsten pixelated collimator, the spatial resolution was 4.4-mm FWHM 40 mm from the collimator surface, and the sensitivity was ∼0.05%. Phantom and small animal images were successfully obtained with our developed gamma camera. CONCLUSIONS: These results confirmed that the developed pixelated GSO gamma camera has potential as an effective instrument for low energy gamma photon imaging.

Metabolic tumor volume of metastatic lymph nodes and survival after total laryngectomy in laryngeal and hypopharyngeal cancer.

OBJECTIVES: The prognostic value of metabolic tumor volume (MTV) in locally advanced laryngeal or hypopharyngeal cancer is established in the setting of chemoradiotherapy, while it remains unknown in the setting of upfront total laryngectomy. MATERIALS AND METHODS: We retrospectively analyzed 88 patients receiving total laryngectomy and neck dissection, using Cox regression models. RESULTS AND CONCLUSION: Variables related to metastatic lymph node were associated with overall survival, whereas those related to primary tumor were not. In multivariable models, MTV of metastatic lymph nodes (N-MTV) as a continuous variable (Akaike's information criterion (AIC), 277.5) was equivalent to pathological nodal status (AIC, 278.2; P = 0.40), and superior to pathological nodal classification as an ordinal variable (AIC, 281.4; P < 0.05) in ability of predicting death. The risk of death was increased by 1.2-fold (95% confidence interval (CI), 1.0-1.4; P = 0.03) every 10-ml increment of N-MTV, while patients with pN+ disease were at a higher risk of death by 2.9-fold (95% CI, 1.0-12.2; P < 0.05) compared with patients with pN0 disease. Using recursive partitioning analysis (RPA), we classified the patients as having a low, intermediate, or high risk of death on the basis of N-MTV and extranodal extension (ENE). This RPA classification system exhibited greater concordance with overall survival than the classification considering pathological nodal status and ENE (AIC, 275.8 versus 281.4; P = 0.02). In the setting of upfront total laryngectomy, N-MTV is a critical predictor of mortality. A staging system in which N-MTV is incorporated may better inform adjuvant treatment decisions.

Effect of CT acquisition parameters in the detection of subtle hypoattenuation in acute cerebral infarction: a phantom study.

BACKGROUND AND PURPOSE: We evaluated the effects of varying tube voltage, current per rotation, and section thickness on detectability of 2- and 4-Hounsfield unit (HU) differences on brain CT between normal and ischemic gray matter within 6 hours of ischemia onset, by using a low-contrast phantom. METHODS: The phantom with an attenuation of 36 HU corresponding to normal gray matter contained 2 sets of spheres (34 HU and 32 HU) corresponding to the early CT signs of ischemic brain and complete infarction, respectively. The reproducibility of the CT numbers and the contrast-to-noise ratio (CNR), defined as the CT number difference between the background (36 HU) and the spheres (34 HU or 32 HU) divided by the SD of the background CT number were measured. Five radiologists rated the phantom images for detection of the low-contrast spheres by visual inspection. RESULTS: The CT numbers were reproducible within 1 HU with a tube current of > or =150 mAs at 120 kVp. The CNRs for the 34- and 32-HU spheres were positively correlated with the tube voltage, tube current per rotation, and the section thickness. A CNR of 1.0 was obtained for the 34-HU sphere when scanning was conducted with a section thickness of 10 mm at 120 kVp and 700 mAs, or 135kVp and 450 mAs, respectively. A significant improvement of the accuracy of detection was found with increasing tube current, tube voltage per rotation, and section thickness. CONCLUSION: Our study indicated that the 2-HU hypoattenuation corresponding to the early CT sign of acute ischemic stroke can be detected by using appropriate parameter settings.

Diagnostic and Prognostic Value of 11C-Methionine PET for Nonenhancing Gliomas.

BACKGROUND AND PURPOSE: Noninvasive radiologic evaluation of glioma can facilitate correct diagnosis and detection of malignant transformation. Although positron-emission tomography is considered valuable in the care of patients with gliomas, (18)F-fluorodeoxyglucose and (11)C-methionine have reportedly shown ambiguous results in terms of grading and prognostication. The present study compared the diagnostic and prognostic capabilities of diffusion tensor imaging, FDG, and (11)C-methionine PET in nonenhancing gliomas. MATERIALS AND METHODS: Thirty-five consecutive newly diagnosed, histologically confirmed nonenhancing gliomas that underwent both FDG and (11)C-methionine PET were retrospectively investigated (23 grade II and 12 grade III gliomas). Apparent diffusion coefficient, fractional anisotropy, and tumor-to-normal tissue ratios of both FDG and (11)C-methionine PET were compared between grade II and III gliomas. Prognostic values of these parameters were also tested by using progression-free survival. RESULTS: Grade III gliomas showed significantly higher average tumor-to-normal tissue and maximum tumor2-to-normal tissue than grade II gliomas in (11)C-methionine (P = .013, P = .0017, respectively), but not in FDG-PET imaging. There was no significant difference in average ADC, minimum ADC, average fractional anisotropy, and maximum fractional anisotropy. (11)C-methionine PET maximum tumor-to-normal tissue ratio of 2.0 was most suitable for detecting grade III gliomas among nonenhancing gliomas (sensitivity, 83.3%; specificity, 73.9%). Among patients not receiving any adjuvant therapy, median progression-free survival was 64.2 ± 7.2 months in patients with maximum tumor-to-normal tissue ratio of <2.0 for (11)C-methionine PET and 18.6 ± 6.9 months in patients with maximum tumor-to-normal tissue ratio of >2.0 (P = .0044). CONCLUSIONS: (11)C-methionine PET holds promise for World Health Organization grading and could offer a prognostic imaging biomarker for nonenhancing gliomas.

Measurement of the ratio of cerebral oxygen consumption to glucose utilization by positron emission tomography: its consistency with the values determined by the Kety-Schmidt method in normal volunteers.

The regional interrelationship between cerebral oxygen consumption (CMRO2) and cerebral glucose utilization (CMRGlc) was studied in normal subjects using positron emission tomography (PET) and the 15O steady-state inhalation and the [18F]fluoro deoxyglucose method. The use of standard sets of rate constants and the model lumped constant of 0.52 as well as the regional blood-brain partition coefficient for water and the blood volume correction for oxygen extraction fraction provided a CMRO2/CMRGlc ratio of 4.89 in the cortical gray matter, 5.27 in the basal ganglia and 5.82 in the centrum semiovale (white matter). The values of CMRO2/CMRGlc for the basal ganglia and the white matter were consistent with those reported for the whole brain with the Kety-Schmidt method. There was no significant difference in the CMRO2/CMRGlc between the basal ganglia and the white matter indicating the similar nature of in vivo oxidative metabolism of glucose in neuron-rich region and glial cell-rich region.

Changes in human regional cerebral blood flow and cerebral blood volume during visual stimulation measured by positron emission tomography.

The hemodynamic mechanism of increase in cerebral blood flow (CBF) during neural activation has not been elucidated in humans. In the current study, changes in both regional CBF and cerebral blood volume (CBV) during visual stimulation in humans were investigated. Cerebral blood flow and CBV were measured by positron emission tomography using H(2)(15)O and (11)CO, respectively, at rest and during 2-Hz and 8-Hz photic flicker stimulation in each of 10 subjects. Changes in CBF in the primary visual cortex were 16% +/- 16% and 68% +/- 20% for the visual stimulation of 2 Hz and 8 Hz, respectively. The changes in CBV were 10% +/- 13% and 21% +/- 5% for 2-Hz and 8-Hz stimulation, respectively. Significant differences between changes in CBF and CBV were observed for visual stimulation of 8 Hz. The relation between CBF and CBV values during rest and visual stimulation was CBV = 0.88CBF(0.30). This indicates that when the increase in CBF during neural activation is great, that increase is caused primarily by the increase in vascular blood velocity rather than by the increase in CBV. This observation is consistent with reported findings obtained during hypercapnia.

Regional differences in cerebral vascular response to PaCO2 changes in humans measured by positron emission tomography.

Hypercapnia and hypocapnia produce cerebral vasodilation and vasoconstriction, respectively. However, regional differences in the vascular response to changes in Paco2 in the human brain are not pronounced. In the current study, these regional differences were evaluated. In each of the 11 healthy subjects, cerebral blood flow (CBF) was measured using 15O-water and positron emission tomography at rest and during hypercapnia and hypocapnia. All CBF images were globally normalized for CBF and transformed into the standard brain anatomy. t values between rest and hypercapnia or hypocapnia conditions were calculated on a pixel-by-pixel basis. In the pons, cerebellum, thalamus, and putamen, significant relative hyperperfusion during hypercapnia was observed, indicating a large capacity for vasodilatation. In the pons and putamen, a significant relative hypoperfusion during hypocapnia, that is, a large capacity for vasoconstriction, was also observed, indicating marked vascular responsiveness. In the temporal, temporo-occipital, and occipital cortices, significant relative hypoperfusion during hypercapnia and significant relative hypoperfusion during hypocapnia were observed, indicating that cerebral vascular tone at rest might incline toward vasodilatation. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve by hypercapnia and in the correction of CBF measurements for variations in subjects' resting Paco2.

Human cerebral glucose metabolism determined by positron emission tomography: a revisit.

The cerebral glucose utilization rate was studied for 27 normal volunteers with 18F-deoxyglucose positron emission tomography (PET). The scanner has a spatial resolution of 6-7 mm and contains corrections for scatter, attenuation, and random coincidences. The lumped constant (tracer-to-glucose dynamic uptake ratio) was determined by comparing the average global uptake of tracer in representative slices with average glucose utilization rates measured by the Kety-Schmidt method as reported in the literature. The resulting value of 0.50 is in excellent agreement with a recent direct determination done by arterial and jugular bulb blood sampling. Gray and white matter values of glucose utilization in various areas of the brain were determined by placing small regions of interest over various cortical, basal, and white matter structures. These values are within 20% of published autoradiographic data on the macaque monkey. The average ratio of gray to white glucose utilization was 2.9, compared with a range of 3-5 for the monkey study and 1.6-2.2 reported in previous PET studies. The effect of instrumental errors on the results is analyzed and discussed.

Photic stimulation study of changing the arterial partial pressure level of carbon dioxide.

To investigate the effect of the level of baseline cerebral blood flow (CBF) on local CBF augmentation by activation, we have used positron emission tomography to measure regional CBF (rCBF) in 12 normal volunteers with and without photic stimulation during hypocapnia, normocapnia, and hypercapnia. The increase in rCBF in the primary visual cortex by photic stimulation was 10.8 +/- 3.1, 18.6 +/- 9.3, and 19.5 +/- 6.1 ml 100 ml-1 min-1 in hypo-, normo-, and hypercapnia, respectively. The increase was significantly smaller in hypocapnia than in normocapnia (p < 0.005). The fractional CBF increase caused by the photic stimulation was the same in all breathing conditions. This result indicates that the magnitude of the CBF increase induced by neuronal activity correlates proportionally with the level of baseline CBF.

Glucose utilization rate versus brain size in humans.

Cerebral glucose metabolic rates were measured in 23 normal volunteers by studying the uptake of 18F-deoxyglucose with positron emission tomography (PET). These values were correlated against a brain-size index obtained from the PET images by measuring the lateral and anteroposterior brain diameters. There was a significant negative correlation (p less than 0.001), which corresponds, within the statistical uncertainty, to an inverse proportionality of glucose metabolic rate and brain volume. The variation with brain size accounted for approximately one-half of the total intersubject variance. Measurements on phantoms of different sizes and analyses of instrumental errors failed to uncover any artifactual reason for the correlation.

Long-term positron emission tomography evaluation of slowly progressive gliomas.

Non-invasive positron emission tomography (PET) was performed to identify changes in blood flow and metabolism, specific to early stages of tumour occurrence or recurrence. 2 patients with slowly progressive gliomas from early to late stages of tumour development were analysed by serial PET measurements of circulation and metabolism using 15O-gas and 18F-fluorodeoxyglucose. PET revealed a persistent depression of oxygen metabolism, as indicated by the regional oxygen extraction fraction or metabolic rate of oxygen, in the regions where tumours were later found. Abnormal blood flow and metabolism may precede the morphological changes detected by computed tomography (CT) in patients with gliomas.

Clinical assessment of therapeutic effects on cancer using 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography: preliminary study of lung cancer.

Using positron emission tomography, we studied the tumor uptake of 18F-2-fluoro-2-deoxy-D-glucose (18FDG) in five lung cancer patients before and after anti-cancer therapy (radiotherapy and/or chemotherapy). The tumor uptake of 18FDG was classified as positive and negative; the former, by increasing the uptake of 18FDG with time, and the latter, by decreasing or the constant uptake of 18FDG. Before therapy, all cases tested positive. After therapy, three cases were negative and two cases remained positive. All negative cases corresponded to complete second 18FDG study. Our findings in the 18FDG study correlate with the clinical results. 18FDG is a promising method for assessing therapeutic effects on cancer clinically.

Estimation of absorbed doses in humans due to intravenous administration of fluorine-18-fluorodeoxyglucose in PET studies.

Radiation absorbed doses due to intravenous administration of fluorine-18-fluorodeoxyglucose in positron emission tomography (PET) studies were estimated in normal volunteers. The time-activity curves were obtained for seven human organs (brain, heart, kidney, liver, lung, pancreas, and spleen) by using dynamic PET scans and for bladder content by using a single detector. These time-activity curves were used for the calculation of the cumulative activity in these organs. Absorbed doses were calculated by the MIRD method using the absorbed dose per unit of cumulated activity, "S" value, transformed for the Japanese physique and the organ masses of the Japanese reference man. The bladder wall and the heart were the organs receiving higher doses of 1.2 x 10(-1) and 4.5 x 10(-2) mGy/MBq, respectively. The brain received a dose of 2.9 x 10(-2) mGy/MBq, and other organs received doses between 1.0 x 10(-2) and 3.0 x 10(-2) mGy/MBq. The effective dose equivalent was estimated to be 2.4 x 10(-2) mSv/MBq. These results were comparable to values of absorbed doses reported by other authors on the radiation dosimetry of this radiopharmaceutical.

Regional cerebral blood flow measurement with iodine-123-IMP autoradiography: normal values, reproducibility and sensitivity to hypoperfusion.

UNLABELLED: We recently proposed a simplified technique for measuring regional cerebral blood flow (rCBF) using the [123I]N-isopropyl-p-iodoamphetamine (IMP) autoradiographic (ARG) method with SPECT (the IMP-ARG method). We examined normal values of rCBF and the reproducibility and sensitivity to hypoperfusion in stroke patients using this method. METHODS: By using a standard arterial input, a single static scan, a fixed distribution volume (Vd) and one-point arterial blood sampling, we measured rCBF in 39 normal volunteers (19 men and 20 women; mean ages 61 +/- 11 yr for the men and 60 +/- 12 yr for the women). Eighteen neurologically stable patients with prior stroke (mean age = 65 +/- 11 yr) were studied twice at a mean interval of 97 days. In 16 patients (7 men and 9 women, mean age = 63 +/- 5 yr) with subarachnoid hemorrhage, rCBF was measured 1-2 wk after onset. Cerebral vasospasm was evaluated by repeated angiography. The mean rCBF in the vasospastic area was compared with that in a nonvasospastic area. RESULTS: The mean rCBFs of the cerebral cortex and centrum semiovale in the volunteers were 33.0 +/- 5.1 ml/100 g/min and 25.0 +/- 4.5 ml/100 g/min, respectively. There was no age-dependent change in rCBF, but the women showed significantly higher cortical rCBF than the men (p < 0.05). In the stroke patients, the whole-brain CBF values showed high reproducibility, with high correlations between those obtained at the first and second studies (y = -3.5 + 1.03x; r = 0.90; p < 0.001). In the subarachnoid hemorrhage patients, the vasospastic area showed significantly lower rCBF than the normal cortical rCBF (p < 0.01) and the nonvasospastic area (p < 0.01). Brain regions with rCBF levels below 20 ml/100 g/min showed infarction on the follow-up CT scan. CONCLUSION: The IMP-ARG method is reproducible, sensitive to hypoperfusion and feasible for the quantitative evaluation of rCBF in routine clinical practice.

Parapharyngeal meningioma extending from the intracranial space evaluated by FDG PET.

We report a rare case of parapharyngeal meningioma extending from the intracranial space evaluated by PET with [18F]-2-fluorodeoxyglucose (FDG). Although the parapharyngeal meningioma had a high rate of glucose metabolism, it was proved to be pathohistologically benign. The high rate of glucose metabolism of the tumor reflected tumor aggressiveness well because the tumor grew in a relatively short time.

Technetium-99m-ECD brain SPECT in misery perfusion.

UNLABELLED: Discordant findings of 99mTc-methyl cysteinate dimer (99mTc-ECD) brain distribution have been reported when brain tissue is supplied by excess blood flow. We evaluated changes in 99mTc-ECD brain activity in the opposing pathological state, in which cerebral blood flow (CBF) is more profoundly impaired than metabolism, and analyzed the relationship of 99mTc-ECD activity with CBF and metabolism to investigate the dominant regulating factor on 99mTc-ECD distribution. METHODS: Twelve patients with unilateral intracranial steno-occlusive diseases were evaluated using dynamic and static 99mTc-ECD SPECT. Relative 99mTc-ECD activities and the retention ratio of the affected and unaffected cortices were compared with CBF and oxygen metabolism obtained by PET. Change in the relationships until 1 hr after tracer injection were also analyzed. RESULTS: Relative 99mTc-ECD activity was significantly correlated with CBF, and the highest correlation was obtained for the first minute of imaging (r = 0.674, p < 0.0010. Fifteen minutes after injection, the correlation coefficient with CBF decreased, whereas higher correlation was observed with the parameter of oxygen metabolism (r = 0.758-0.815, p < 0.001). Changes in the retention ratio were dependent on changes in oxygen metabolism, and the retention ratio for the high oxygen extraction fraction (OEF) area was the same as that for the normal OEF area. CONCLUSION: In addition to CBF, brain distribution on 99mTc-ECD SPECT images is affected by brain metabolism, especially on delayed images after injection. The degree of discrepancy between CBF and metabolism should be considered when interpreting images of the misery perfusion state.

Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT.

UNLABELLED: A method was developed to calculate functional images of regional cerebral blood flow (rCBF) from a single scan using SPECT following intravenous 123I-N-isopropyl-p-iodoamphetamine (IMP) infusion. METHODS: A two-compartment model that includes two parameters of rCBF and regional distribution volume of IMP (Vd) was employed to correct for clearance of IMP from the brain. Using a given input function and a fixed Vd value (30 ml/ml according to an analysis on dynamic SPECT data), a unique value of rCBF was calculated for each pixel of the SPECT image according to the table-look-up procedure. This technique was applied to 15 human subjects, and the calculated rCBF values were compared with those measured by PET. RESULTS: A set of simulation studies demonstrated an optimal SPECT midscan time at 30 to 40 min postinjection of IMP, providing the minimal error sensitivity to the individual difference of the input function (rCBF values with an accuracy of +/- 10%). Another set of simulation suggested validity of fixing the Vd values, i.e., errors in calculated rCBF values were around +/- 7% for a change of Vd of +/- 10%. The measured rCBF values obtained from 15 human subjects were independent on the SPECT scan time. The calculated rCBF values also agreed well with those obtained by the nonlinear least-squares fitting analysis that were obtained from the dynamic SPECT scan and the frequent arterial blood sampling and measurement of lipophilic fraction for each sample (0.54 + 0.88x, r = 0.86), suggesting the validity of the simplified procedures in this method. CONCLUSION: These observations suggested the validity of this method as a clinical tool for quantitative measurement of rCBF.

Differential diagnosis of lung tumor with positron emission tomography: a prospective study.

To predict the nature of non-calcifying lung tumors, we performed a prospective study of 46 cases with L-[methyl 11C]methionine (MET, 24 cases) and 18F-fluorodeoxyglucose (FDG, 22 cases) using positron emission tomography (PET). Mean tumor/muscle radioactivity ratios are 5.3 +/- 2.0 (n = 14) for malignant and 1.9 +/- 0.9 (n = 10) for benign with MET (p less than 0.001), and 4.4 +/- 2.2 (n = 12) and 1.5 +/- 0.3 (n = 10), respectively, with FDG (p less than 0.001). The ratios indicate that malignant tumors have higher metabolic demand than benign lesions. Tumors less than 1 cm in diameter were difficult to accurately evaluate due to PET resolution. Compared to the diagnosis at pathology, the MET study showed a sensitivity of 93% (13/14), a specificity of 60% (6/10), and an accuracy of 79% (19/24). The FDG study showed 83% (10/12), 90% (9/10), 86% (19/22), respectively. No significant differences were observed between the two tracers. This study suggests that PET studies using either MET or FDG may be very useful for the differential diagnosis of lung tumors.

6-[18F]fluoro-L-fucose: a possible tracer for assessing glycoconjugate synthesis in tumors with positron emission tomography.

The potential of 6-[18F]fluoro-L-fucose (6-[18F]FFuc) for assessing glycoconjugate synthesis in tumors with positron emission tomography (PET) was investigated. Using the tissue sampling method with five tumor models, different time-radioactivity profiles were found: a nearly constant level in Lewis lung carcinoma (3LL) and different clearance patterns in others. Rapid clearance in normal tissues resulted in preferable uptake ratios for tumor imaging of brain and pancreas. Metabolic studies and the L-fucose loading effects on the tissue uptake proved the tracer to be a biochemically active L-fucose analog. Imaging of the intracranial rat glioma and 3LL in lungs or hepatomas in mice by autoradiography (ARG) and intramuscular VX-2 carcinoma in rabbits by PET was demonstrated. Using double-radionuclide ARG, similar distribution images of 6-[18F]FFuc and 14C-L-fucose but different tumor-to-liver uptake ratios were found. A metastasis model seemed to show a higher uptake of both tracers as compared to a primary tumor model.

D2-dopamine receptor specific brain uptake of carbon-11-labeled YM-09151-2.

The in vivo D2-receptor specific brain uptake of N-[(2RS,3RS)-1-benzyl-2- methyl-3-pyrrolidinyl]-5-chloro-2-methoxy-4-[11C]methylaminobenzamide ([11C]YM-09151-2), was investigated. In rat brain the high uptake of [11C]YM-09151-2 in striatum was displaced with sulpiride, spiroperidol, and YM-09151-2. SCH-23390 and ritanserin, D1-dopamine and S2-serotonin antagonists, showed no effect on the distribution of [11C]YM-09151-2. In the striatum at 60 min, 95% of the radioactivity was detected as [11C]YM-09151-2 by high performance liquid chromatography. On the other hand, 41% of 11C in the plasma at 60 min was observed as metabolites. In vivo autoradiography showed a high uptake of [11C]YM-09151-2 in the striatum and in the nucleus accumbens of rat brain. A high uptake of radioactivity was also found in the canine basal ganglia with positron emission tomography. The uptake was reduced by pretreatment with spiroperidol. The present results demonstrate that [11C]YM-09151-2 is a D2 receptor specific compound and is a potential in vivo tracer for measuring D2 receptors.