[Influence of Reconstruction FOV and Matrix Size on the Quantitative Accuracy of FDG-PET: Comparison between OSEM and Bayesian Penalized Likelihood].

PURPOSE: Field of view (FOV) and matrix size determine the pixel size of positron emission tomography (PET) images; however, the effect of any variation in these parameters on the quantitative accuracy is unclear. The FOV and matrix size of PET images are adjusted as per each clinical objective. Therefore, this study aimed to evaluate the quantitative accuracy of PET images under different FOV and matrix sizes. METHOD: A National Electrical Manufacturers Association (NEMA) body phantom set was filled with 18F-FDG solution, and imaging data were acquired for 30 min. Images were reconstructed using ordered subset expectation maximization (OSEM) and Bayesian penalized likelihood (BPL), both of which were combined with point spread function (PSF) and time of flight (TOF). In each reconstruction method, the image parameters were set to the following: FOV, 20-70 cm; matrix size, 128×128 to 384×384; and pixel size, 1-3 mm. The images were evaluated by physical assessment of the recovery coefficient (RC) and maximum standardized uptake value ratio (SUVmax ratio). RESULT: The RC of OSEM images was not affected by changes in FOV, whereas the RC of BPL images decreased in small spheres, when FOV was 20 and 30 cm. The SUVmax ratio of the OSEM images was not affected by the difference in pixel size. However, the SUVmax ratio of BPL images degraded in the 1-mm pixel size; this influence was observed only when the FOV was changed. Conclusion: BPL images reconstructed using a small FOV might degrade the quantitative accuracy of small spheres.

Ten-year prospective evaluation of whole-body cancer screening with multiple modalities including [18F]fluorodeoxyglucose positron emission tomography in a healthy population.

PURPOSE: To prospectively evaluate the value of whole-body cancer screening with multiple modalities including FDG-PET in a healthy population. METHODS: The study was conducted in 1197 healthy individuals aged ≥ 35 years at enrollment between August 2003 and July 2004. All participants were scheduled to receive annual whole-body cancer screening five times (screening period) with subsequent long-term follow-up (follow-up period). The endpoints of the study were definitive cancer diagnosis, cancer-related death, and all-cause death. RESULTS: The follow-up rate was 99.8% for the screening period and 96.2% for the follow-up period. Forty-five cancers were confirmed during the screening period (August 2003 to July 2009), and 37 of the 45 were detected by the screening. Fourteen of the 45 were PET positive. Sixteen, 5, 4, 9 and 11 cancers were confirmed after the first, the second, the third, the fourth, and the fifth (took 2 years) screening, respectively. Eight participants died, of whom five died of cancer. The rate of cancer incidence (per 100,000) of 628.7 (95% confidence interval [CI] 445.0-812.4) was significantly high, and the rates of cancer mortality and all-cause mortality of 69.9 (95% CI 8.6-131.1) and 111.8 (95% CI 34.3-189.2), respectively, were significantly low, compared with the corresponding rates of 379.3, 138.2 and 354.2, respectively, in the age-rank- and sex-matched general population. During the follow-up period (August 2009 to July 2013), 37 cancers were confirmed and 30 of the 37 were detected. Seven participants died, of whom three died of cancer. The rate of cancer incidence was 809.6 (95% CI 548.7-1070.5). The rates of cancer mortality and all-cause mortality of 65.6 (95% CI 0-139.9) and 153.2 (95% CI 39.7-266.6), respectively, were significantly low compared with 190.1 and 462.3, respectively, in the general population. CONCLUSION: Cancer detection by PET alone was limited. While the high cancer incidence was attributed to the extensive screening, the low cancer and all-cause mortality may indicate the potential value of this type of cancer screening. Cancer incidence increases with aging and it has been shown that continuous screening may reduce the risk caused by the cancer progression.

[Impact of point spread function correction in standardized uptake value quantitation for positron emission tomography images: a study based on phantom experiments and clinical images].

While point spread function (PSF)-based positron emission tomography (PET) reconstruction effectively improves the spatial resolution and image quality of PET, it may damage its quantitative properties by producing edge artifacts, or Gibbs artifacts, which appear to cause overestimation of regional radioactivity concentration. In this report, we investigated how edge artifacts produce negative effects on the quantitative properties of PET. Experiments with a National Electrical Manufacturers Association (NEMA) phantom, containing radioactive spheres of a variety of sizes and background filled with cold air or water, or radioactive solutions, showed that profiles modified by edge artifacts were reproducible regardless of background µ values, and the effects of edge artifacts increased with increasing sphere-to-background radioactivity concentration ratio (S/B ratio). Profiles were also affected by edge artifacts in complex fashion in response to variable combinations of sphere sizes and S/B ratios; and central single-peak overestimation up to 50% was occasionally noted in relatively small spheres with high S/B ratios. Effects of edge artifacts were obscured in spheres with low S/B ratios. In patient images with a variety of focal lesions, areas of higher radioactivity accumulation were generally more enhanced by edge artifacts, but the effects were variable depending on the size of and accumulation in the lesion. PET images generated using PSF-based reconstruction are therefore not appropriate for the evaluation of SUV.

Progression from unilateral to bilateral parkinsonism in early Parkinson disease: implication of mesocortical dopamine dysfunction by PET.

UNLABELLED: It is still unclear why some early Parkinson disease (PD) patients with unilateral parkinsonism develop bilateral parkinsonism soon after the diagnosis is made as Hoehn and Yahr (HY) stage 1 and others remain stable for a long time. Here, we examined in vivo changes in the brain dopaminergic system using PET with a dopamine transporter radiotracer, (11)C-2-B-carbomethoxy-3B-(4-fluorophenyl) tropane ((11)C-CFT), to elucidate the pathophysiologic characteristics of the dopamine system in early converters. METHODS: Twelve drug-naïve PD patients with HY stage 1 disease and 8 age-matched healthy subjects participated in this study. Clinical evaluation of their parkinsonism was performed monthly until their HY stage 1 (unilateral parkinsonism) disease had become stage 2 (bilateral parkinsonism) disease according to the Unified Parkinson Disease Rating Scale. The endpoint of the follow-up study was the time of the conversion. Region-of-interest analysis was used to examine (11)C-CFT binding in the mesocortical (nucleus accumbens, caudate, orbitofrontal cortex) and nigrostriatal (putamen) dopamine projection regions. Multiregression analyses between these PET data and clinical parameters were performed within the PD group. RESULTS: Between-group comparisons showed that, irrespective of the duration of conversion, all PD patients clinically diagnosed at HY stage 1 had a significant reduction in (11)C-CFT binding in the bilateral striatum (affected, -46%; unaffected, -35%). Regression analysis showed that the level of (11)C-CFT binding in the nucleus accumbens and orbitofrontal cortex on the unaffected side was significantly positively correlated with the conversion interval. This positive correlation indicates that the more severe a dysfunction presents in the mesocortical dopamine system on the seemingly intact side, the more rapidly the parkinsonism proceeds to the intact side (bilateral parkinsonism). CONCLUSION: The finding of bilateral reduction in the striatal (11)C-CFT binding even in HY stage 1 PD patients confirms that molecular changes in the dopamine system precede clinical phenotype, suggesting an advantage of PET for detecting an early abnormality of the disease. The spread of parkinsonism to the unaffected side soon after the diagnosis of HY stage 1 PD may be related to the degree of mesocortical dopamine dysfunction.

Single 20-second acquisition of deep-inspiration breath-hold PET/CT: clinical feasibility for lung cancer.

UNLABELLED: This study was designed to compare tumor (18)F-FDG uptake between a single 20-s acquisition of deep-inspiration breath-hold PET/CT and free-breathing PET/CT for lung cancer. METHODS: Before the clinical study, a phantom study was performed to determine the optimum breath-hold time for the PET scan. We studied 47 patients with lung cancer who underwent free-breathing PET/CT with the standard clinical protocol, followed by deep-inspiration breath-hold PET/CT of the thorax. In breath-hold PET/CT, the patients were asked to hold their breath in deep inspiration for 10 s during the CT scan and for 20 s during the PET scan. Maximum tumor (18)F-FDG standardized uptake value (SUVmax) was measured in free-breathing PET and breath-hold PET, and the percentage difference between these 2 values was calculated. RESULTS: Breath-hold PET showed a significant increase in SUVmax, as compared with free-breathing PET (8.26 +/- 4.59 vs. 11.25 +/- 7.24, P < 0.0001). The mean difference in SUVmax was 39.5% +/- 43.4%, and the range was 2.9%-248.3%. The difference in SUVmax was significant when compared between tumors in the upper lung (n = 22) and tumors in the lower lung (n = 25) (24.4% +/- 17.7% vs. 52.9% +/- 54.3%, P = 0.0077). The mean tumor size of the group with a high SUVmax difference (n = 13) was significantly smaller than that of the group with a low SUVmax difference (n = 34) (2.45 +/- 0.87 cm vs. 3.21 +/- 1.22 cm, P = 0.043), using a cutoff of 39.5%. CONCLUSION: The single 20-s acquisition of breath-hold PET/CT enabled more precise measurement of SUVmax, especially in the lower lung field and for small tumors, which may be affected by respiratory motion. This technique is feasible in the clinical setting and requires only a minor increase in examination time.

Prognostic value of 18F-FDG PET in patients with head and neck squamous cell cancer.

OBJECTIVE: This study was designed to assess whether tumor uptake of (18)F-FDG (FDG) expressed as the standardized uptake value (SUV) can be used to predict survival in patients with head and neck cancer. Furthermore, a prognostic maximum SUV was determined with univariate and bivariate analyses. CONCLUSION: Low SUVs ( 7.0). In the Cox proportional hazards model, tumor SUV was a significant and independent predictor of local control (p = 0.022) and disease-free survival (p = 0.019). In addition, in the group of high SUV, high T stage was more associated with poorer outcome than low T stage (p = 0.0502). Therefore, patients with higher tumor FDG uptake should be considered for a more aggressive treatment approach.

[Visualization of prostate cancer with 11C-choline positron emission tomography (PET): localization of primary and recurrent prostate cancer].

A total of 33 11C-choline positron emission tomography scans for 23 patients with prostate cancer were performed to elucidate the localization of primary site within the prostate gland (primary group) and of recurrent site after radical treatment (recurrent group) from 2000 to 2005. As a control group, one scan for benign prostate hyperplasia and 3 scans for bladder cancer were also studied. Mean PSA values of 14 scans in the primary group and 19 scans in the recurrent group were 39.8 ng/ml (range 1.6-150) and 5.0 ng/ml (range < 0.2-11), respectively. The primary cancer could be visualized as a hot spot within the prostate gland in 10 out of 14 scans and histopathological analysis of biopsy and prostatectomy specimens verified the correct laterality. Positive scans were demonstrated in 2 out of 4 local recurrent sites, 4 out of 4 lymph node recurrent sites and 4 out of 4 bone recurrent sites with a mean PSA value of 6.22 ng/ml (range 2.3-11). Four scans with a PSA value of 2.3 ng/ml or less, no positive spot was demonstrated. These 4 scans consisted of 2 false negative and 2 true negative studies. 11C-choline PET seems to be useful to detect primary prostate cancer and could play a complementary role for conventional imaging methods in recurrent site staging.

Striatal D2 receptor availability after shunting in idiopathic normal pressure hydrocephalus.

UNLABELLED: Gait disturbance in idiopathic normal pressure hydrocephalus (iNPH) is reminiscent of parkinsonism. Our recent PET study showed reduction in postsynaptic D(2) receptor binding concomitant with a normality of presynaptic dopamine transporter binding. Here, we investigated the plasticity of D(2) receptor in treating iNPH patients with ventriculoperitoneal (VP) shunting using PET with (11)C-raclopride and discuss the contribution of D(2) receptor to the pathophysiology of iNPH. METHODS: Eight iNPH patients participated in this study. After evaluation of their neuropsychologic abilities, all patients underwent 3-dimensional MRI and quantitative PET measurements twice before and 1 mo after VP shunting. MRI-based morphometric analyses were performed to examine postoperative variations of the ventricles. Estimation of binding potential (BP) for (11)C-raclopride was based on Logan plot analysis. Region-of-interest analysis was used to examine changes in (11)C-raclopride BP in the striatum. A 2-tailed paired t test was used for evaluating changes in PET and MRI parameters between conditions, and correlation analysis was used to investigate clinicopathophysiologic relevance (clinical vs. in vivo findings). RESULTS: Clinical evaluation revealed significant recovery in a 5-m back-and-forth navigation test and an affect test and a mild increase in Mini-Mental State Examination scores after VP shunting. Significant postoperative increases in (11)C-raclopride BP were found in the nucleus accumbens and dorsal putamen, and the increases were significantly associated with emotional (Spearman rank r = 0.66, P < 0.05) and navigational improvement (r = 0.72, P < 0.05), respectively. The (11)C-raclopride BP increase in the striaum as a whole correlated significantly with improvement in general cognitive ability. There was a mild ventricular shrinkage after surgery, albeit there was no correlation of its size with clinical and PET parameters. CONCLUSION: Striatal upregulation of D(2) receptor after VP shunting is associated with amelioration of hypokinetic gait disturbance and anhedonic mentation in iNPH patients, indicating that the effect of VP shunting may reside in noninhibition of functionally suppressed D(2) receptor in the striatum. D(2) receptor responsiveness may indicate a mechanism for iNPH pathophysiology.

In vivo presynaptic and postsynaptic striatal dopamine functions in idiopathic normal pressure hydrocephalus.

Differentiation of impaired gait seen in idiopathic normal pressure hydrocephalus (iNPH) from parkinsonian gait is sometimes a great challenge and important for future medication in the clinical setting. To investigate dopaminergic contribution to its pathophysiology, two aspects of the trans-synaptic dopamine functions in the striatal region in eight iNPH patients naïve to dopaminergic drugs were examined using positron emission tomography with a presynaptic marker [11C]CFT ([11C]2-beta-carbomethoxy-3beta-(4-fluorophenyl) tropane) that binds to dopamine transporter and a postsynaptic marker [11C]raclopride that binds to D2 receptor. Quantitative values of binding potentials (BPs) for [11C]CFT and [11C]raclopride were compared between patients and eight age-matched healthy subjects. The BPs and magnetic resonance imaging-based morphometric measures in iNPH were used for correlation analyses between the magnitude of binding of these in vivo markers and clinical severity of the patients. Analysis of variance showed significant reduction in [11C]raclopride binding in the putamen and nucleus accumbens (P<0.05, corrected for multiple comparison) and unchanged striatal [11C]CFT binding in iNPH. The dorsal putamen [11C]raclopride binding correlated negatively with gait severity (r=0.720, P<0.05), and the nucleus accumbens [11C]raclopride binding correlated positively with emotional recognition score (r=0.727, P<0.05) in the disease group. No significant relationship was observed between BPs and morphometric measures. The current result of the postsynaptic D2 receptor reduction along with preserved presynaptic activity in the nigrostriatal dopaminergic system reflects a pathophysiology of iNPH. Postsynaptic D2 receptor hypoactivity in the dorsal putamen may predict the severity of gait impairment in iNPH.

Usefulness of positron emission tomography (PET) in a retroperitoneal primary non-seminomatous germ cell tumor: a case report.

A 32-year-old Japanese man was admitted complaining of palindromic fever and abdominal pain. Computed tomography (CT) revealed retroperitoneal mass and positron emission tomography (PET) demonstrated massive radiotracer uptake in this tumor. Serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) were 4,760 ng/ml, 6,000 mIU/ml, respectively. Biopsy specimen from the tumor showed non-seminomatous germ cell tumor. The International Germ Cell Cancer Collaborative Group (IGCCCG) staging system indicated this case as an intermediate prognosis group. After three cycles of bleomycin, etoposide and cisplatin (BEP) therapy, CT revealed a degenerated residual mass. Serum levels of tumor markers were normalized completely and PET showed no radiotracer uptake in the retroperitoneal lesion. Although he did not receive further chemotherapy and lymph nodes were not dissected, he was free of disease for two years.

[Measurement of radiation exposure to a PET institution driver from patients injected with FDG].

With the recent increase in FDG-PET examinations, concern has mounted regarding radiation exposure to hospital staff and the general public from patients injected with FDG. Because our PET institution is located 15 km from the hospital that provides these examinations, a driver has been designated to transport patients injected with FDG. This study was designed to measure the radiation dose to the driver from these patients (n=28) and to compare it with the estimated dose. A pocket dosimeter was used to measure radiation exposure to the driver. When the distances between the driver and patient were 1.1 m and 1.9 m, mean measured doses were 7.31 microSv and 2.26 microSv, respectively, while mean estimated doses were 8.61 microSv and 2.82 microSv, respectively, per trip. It was presumed that maximum radiation exposure per year was between 3.02 mSv (1.1 m) and 0.92 mSv (1.9 m). According to our data, the measured dose was 20% lower than the estimated dose. This discrepancy may be due to the difference between the volume source (measured dose) and point source (estimated dose).

Preoperative positron emission tomography with fluorine-18-fluorodeoxyglucose is predictive of prognosis in patients with hepatocellular carcinoma after resection.

BACKGROUND: Hepatocellular carcinomas (HCCs) accumulate fluorine-18 fluorodeoxyglucose (FDG) to various degrees. The standardized uptake values (SUVs) of FDG-positron emission tomography (PET) in high-grade HCCs are significantly higher than those in low-grade HCCs. AIM: The aim of this study was to evaluate the possible usefulness of FDG-PET in predicting the prognosis of HCC patients after resection. We analyzed the relationship between the tumor to non-tumor SUV ratios (SUV ratio) and surgical outcome in 31 patients. RESULTS: Of the 31 cases of HCC studied, seven (23%) exhibited SUV ratios greater than 2, as the cutoff value. The percentage of patients with poorly differentiated HCC was greater in the higher SUV ratio group (SUV ratio >2) than in the lower SUV ratio group (SUV ratio <2) (57 vs. 32%). The overall survival was significantly longer in the lower SUV ratio group than in the higher SUV ratio group (5-year-survival rate: 63 vs. 29% P = 0.006) (median survival time: 2310 vs.182 days). CONCLUSION: The SUV ratio was related significantly to disease-related death as well as other predictive factors, including the number of tumors, the size, stage, and involvement of vessels, and the involvement of the capsule. Consequently, we conclude that the SUV ratio provides information of prognostic relevance in patients with HCC before surgery.

C-choline positron emission tomography in bladder cancer: report of four cases.

Little work has been done with positive emission tomography (PET) in bladder tumors because high urinary excretion of (18)F-FDG makes visualization of the bladder tumor difficult. (11)C-choline has recently been reported as a new tracer which lacks urinary radioactivity. We report the result of (11)C-choline PET in four patients with invasive bladder tumors. In one case, (11)C-choline PET could detect bladder tumor effectively without urinary activity and bone metastasis despite negative bone scintigraphy. On the other hand, an intense accumulation of the tracer in the bladder hampered the interpretation on PET scanning in three patients. The mechanisms of the (11)C-choline accumulation in the bladder were reported to be due to inflammatory and proliferative changes in the mucosa of the bladder from previous catheterization or other factors. Further study is necessary to prove the value of (11)C-choline PET for detecting primary bladder cancer and bone metastasis.

FDG PET for the assessment of myometrial infiltration in clinical stage I uterine corpus cancer.

OBJECTIVE: For surgical planning of uterine corpus cancer, prior knowledge of the depth of myometrial invasion is important. Curative tumour resection is possible in superficial invasion (stages IA and IB), while post-surgical chemotherapy or radiation therapy is required in deep invasion (stage IC). We evaluated the value of positron emission tomography with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG PET) for estimating the myometrial invasion in uterine corpus cancer. METHODS: We studied 22 patients with clinical stage I uterine corpus cancer, who underwent FDG PET prior to surgery. Standardized uptake value (SUV; tracer activity per injected dose normalized to body weight) was calculated on the PET image. PET findings were compared with magnetic resonance imaging (MRI) and the surgical staging. RESULTS: The surgical stage was IA in five, IB in 11 and IC in six patients. SUVs in deep invasion (15.69+/-4.73, 8.83-21.84) were significantly higher than those in superficial invasion (9.09+/-3.29, 2.68-15.41) (P<0.005). Using 12.0 as a cut-off value of SUV for the differentiation of these two groups, PET results were correct in 19 patients but were incorrect in three patients. Although both PET and MRI provided correct staging in 14 patients, only MRI overestimated the myometrial invasion in four patients with stage IB and showed inconclusive findings in one patient with stage IC. Four of these five patients were post-menopausal. CONCLUSIONS: The cut-off value of SUV (=12.0) may be a useful index for the differentiation of superficial invasion and deep invasion. FDG PET may be feasible for predicting the myometrial infiltration of uterine corpus cancer, especially when uterine atrophy makes it difficult at MRI in post-menopausal patients.

[Physical property of emission data in simultaneous emission/transmission acquisition: evaluation for clinical application].

PURPOSE: Although simultaneous emission transmission acquisition (SET) is the ideal method for positron emission tomography (PET) because the same patient position can be used for both emission and transmission scans, the quality of PET images is subject to interference by the cross-contamination of each data. In recent years, segmented attenuation correction of transmission data has made it possible to exclude the contamination from emission data. In the present study using a phantom, the physical property of emission data in SET acquisition was evaluated in comparison with that in separate scan. METHODS: We measured scatter fraction, scatter projection, % random, and noise equivalent count rate in the sinogram. Next, we determined the acquisition time of the SET scan to obtain the same coefficient of variation as the separate scan in reconstructed images. RESULTS: In the evaluation of the strength of the line source, the physical property of emission data in the SET scan seemed inferior to that in separate scan, and SET scanning was not effective enough to reduce the acquisition time of PET examinations. CONCLUSION: SET scanning has the advantage that the same patient position can be used for emission and transmission data; however, further studies may be necessary to apply it to clinical examinations.

Positron emission tomography with 18F-fluoro-2-deoxyglucose for the detection of recurrent ovarian cancer.

BACKGROUND: Recurrent ovarian cancer is refractory and resistant to treatment in most patients, and no effective treatment for it has been established. Starting a treatment when tumors still consist of micro foci may contribute to improvement of prognosis. Therefore, the early diagnosis of relapse is important. METHODS: Among patients with epithelial ovarian cancer in whom initial treatment achieved remission between April 1998 and December 2003, those patients in whom the cancer-related antigen (CA)125 level was increased during the subsequent follow-up period, or those who showed abnormal computed tomography (CT)/magnetic resonance imaging (MRI) findings despite normal CA125 levels, were examined by 18F-fluoro-2-deoxyglucose - positron emission tomography (FDG-PET). We compared the rates of accurate diagnosis of recurrence achieved using CT/MRI, CA125, and FDG-PET in patients with a definitive diagnosis of relapse. RESULTS: We investigated 29 patients with epithelial ovarian cancer. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of FDG-PET were 84.6% (22/26), 100% (3/3), 100% (22/22), 42.9% (3/7), and 86.2% (25/29), respectively. These values were higher than the corresponding values obtained using CT/MRI or CA125 levels. CONCLUSION: FDG-PET may be very useful for identifying sites of recurrent ovarian cancer, although this procedure had a low NPV because of the high rate of false-negative findings for micro or cystic lesions.

11C-choline positron emission tomography in prostate cancer: primary staging and recurrent site staging.

OBJECTIVES: To evaluate the usefulness of 11C-choline positron emission tomography (PET) for primary staging and re-staging of prostate cancer. PATIENTS AND METHODS: 11C-choline PET, a total of 22 scans, was performed on 13 patients with histologically proven prostate cancer in primary staging (n = 6) and recurrent site staging; following radical prostatectomy (n = 5) and following radiation therapy (n = 3). In 1 patient, 11C-choline PET was performed in both primary staging and re-staging. Also, 3 patients histologically proven to have no malignant prostate were included. RESULTS: Because urinary 11C-choline activity was low, it did not interfere with the visualization of pelvic structures. 11C-choline PET visualized normal prostate with a mean SUV of 2.99 (range 2.27-3.68) and primary prostate cancer as a hot spot in 5/6 scans with a mean SUV of 4.21 (range 2.99-6.2). In re-staging, 11C-choline PET was true positive in 9/16 scans and true negative in 2/16 scans. 5/16 scans in 2 patients were false negative with negative conventional imaging. CONCLUSIONS: In primary staging, 11C-choline PET may not be of use because of no reliable differential 11C-choline uptake of BPH and prostate cancer. On the other hand, 11C-choline PET may be of value in recurrent site staging and monitoring for the prostate cancer.