Luigi Gianolli

Physical performance of the new hybrid PET∕CT Discovery-690.

PURPOSE The aim of this work was the assessment of the physical performance of the new hybrid PET∕CT system: Discovery-690. METHODS The Discovery-690 combines a lutetium-yttrium-orthosilicate (LYSO) block detector designed PET tomograph with a 64-slice CT scanner. The system is further characterized by a dedicated powerful computing platform implementing fully 3D-PET iterative reconstruction algorithms. These algorithms can account for time of flight (TOF) information and∕or a 3D model of the PET point spread function (PSF). PET physical performance was measured following NEMA NU-2-2007 procedures. Furthermore, specific tests were used: (i) to measure the energy and timing resolution of the PET system and (ii) to evaluate image quality, by using phantoms representing different clinical conditions (e.g., brain and whole body). Data processing and reconstructions were performed as required by standard procedures. Further reconstructions were carried out to evaluate the performance of the new reconstruction algorithms. In particular, four algorithms were considered for the reconstruction of the PET data: (i) HD = standard configuration, without TOF and PSF, (ii) TOF = HD + TOF, (iii) PSF = HD + PSF, and (iv) TOFPSF = HD + TOF + PSF. RESULTS The transverse (axial) spatial resolution values were 4.70 (4.74) mm and 5.06 (5.55) mm at 1 cm and 10 cm off axis, respectively. Sensitivity (average between 0 and 10 cm) was 7.5 cps∕kBq. The noise equivalent count rate (NECR) peak was 139.1 kcps at 29.0 kBq∕ml. The scatter fraction at the NECR peak was 37%. The correction accuracy for the dead time losses and random event counts had a maximum absolute error below the NECR peak of 2.09%. The average energy and timing resolution were 12.4% and 544.3 ps, respectively. PET image quality was evaluated with the NEMA IEC Body phantom by using four reconstruction algorithms (HD, TOF, PSF, and TOFPSF), as previously described. The hot contrast (after 3 iterations and for a lesion∕background activity ratio of 4:1) for the spheres of 10, 13, 17, and 22 mm was (HD) 29.8, 45.4, 55.4, and 68.1%; (TOF) 39.9, 53.5, 62.7, and 72.2%; (PSF) 28.3, 47.3, 60.4, and 71.8%; (TOFPSF) 43.8, 62.9, 70.6, and 76.4%. The cold contrast for the spheres of 28 and 37 mm was (HD) 62.4 and 65.2%; (TOF) 77.1 and 81.4%; (PSF) 62.0 and 65.2%; (TOFPSF) 77.3 and 81.6%. Similar hot and cold contrast trends were found during the analyses of other phantoms representing different clinical conditions (brain and whole body). Nevertheless, the authors observed a predominant role of either TOF or PSF, depending on the specific characteristics and dimensions of the phantoms. CONCLUSIONS Discovery-690 shows very good PET physical performance for all the standard NEMA NU-2-2007 measurements. Furthermore, the new reconstruction algorithms available for PET data (TOF and PSF) allow further improvements of the D-690 image quality performance both qualitatively and quantitatively.

Value of integrated PET/CT for lesion localisation in cancer patients: a comparative study

The aim of this study was to retrospectively compare the value of integrated PET/CT and separate PET plus morphological imaging studies for lesion localisation in cancer patients. Two different series of consecutive patients who had previously been treated for neoplastic disease were considered. One series consisted of 105 patients who had undergone [18F]fluorodeoxyglucose (FDG) PET/CT (n=70) or [11C]choline PET/CT (n=35) studies (PET/CT group). The other series comprised 105 patients who had undergone FDG PET scan (n=70) or [11C]choline PET scan (n=35) alone; in this series, PET findings were correlated with the results of morphological imaging (MI) studies, i.e. CT (n=92) or MR imaging (n=13) (PET+MI group). Regions of abnormal tracer uptake at PET scanning were classified as ambiguous or unambiguous depending on their precise anatomical localisation. A total of 207 and 196 lesions were found in the PET/CT and PET+MI groups, respectively. The difference in terms of number of lesions per patient detected with the two imaging protocols was not statistically significant (P=0.718). When analysis of lesion localisation was performed, there were 7/207 (3.4%) and 30/196 (15.3%) ambiguous lesions in the PET/CT and PET+MI groups, respectively. The number of ambiguous lesions was significantly higher in the PET+MI group than in the PET/CT group (χ2=15.768, P<0.0001). Comparison of the effect of use of the different tracers on reporting of PET/CT versus PET+MI revealed that the improvement in the final report in [11C]choline PET/CT studies was similar to that observed in [18F]FDG studies. In cancer patients, PET/CT shows higher diagnostic accuracy for lesion localisation than PET plus morphological imaging studies performed independently. This result does not seem to be affected by the type of tracer used.

PET/CT and breast cancer.

During the past decade, the application of positron emission tomography with [18F]fluoro-2-deoxy-d-glucose (FDG-PET) has remarkably improved the management of cancer patients. Nevertheless, the clinical interpretation of FDG-PET scan can be difficult for two main reasons: (1) anatomical localisation of FDG uptake is not easy, (2) normal physiological accumulation of FDG can be misinterpreted as a pathologic area. It has been demonstrated that the visual correlation of PET with morphological procedures, such as computed tomography or magnetic resonance imaging, can improve the accuracy of PET alone. However, the time interval between the two scans, the time employed by the operator and difficulties in co-registering imaging of the abdomen and pelvis make the co-registration of separately obtained images clinically difficult. A novel combined PET/CT system has been built that improves the capacity to correctly localise and interpret FDG uptake. To date only a few studies have been conducted on the potential role of PET/CT in the management of breast cancer patients, but the better performance of this technique compared with PET alone should also be relevant for breast cancer application. In this review, we evaluate the possible impact on breast cancer diagnosis of PET/CT compared with PET alone, with respect to disease re-staging, treatment monitoring, preoperative staging and primary diagnosis. In addition, the possible role of PET/CT for radiotherapy planning is evaluated.

Persistent Renal Hypertrophy and Faster Decline of Glomerular Filtration Rate Precede the Development of Microalbuminuria in Type 1 Diabetes

Soon after the onset of type 1 diabetes, renal hypertrophy and hyperfiltration become manifest, particularly among patients who will subsequently develop diabetic nephropathy. Whether these early renal dysfunctions are involved in the pathogenesis of diabetic nephropathy is currently unclear. We evaluated, during the same day, kidney volume and glomerular filtration rate (GFR) in 146 patients with type 1 diabetes and normal renal function. All the individuals were then monitored for a mean of 9.5 ± 4.4 years for the development of microalbuminuria. Kidney volume and GFR were reevaluated in a subset of 68 patients 4 years after baseline. During follow-up, microalbuminuria developed in 27 of 146 diabetic patients. At baseline, kidney volume (312.8 ± 52.6 vs. 281.4 ± 46.1 vs. 236.8 ± 41.6 ml/1.73 m2, P < 0.05) but not GFR was increased in patients predisposed to microalbuminuria. Risk of progression was higher in patients with increased kidney volume (P = 0.0058). Patients predisposed to microalbuminuria showed a stable increase in kidney volume (P = 0.003), along with a faster decline of GFR (P = 0.01). Persistent renal hypertrophy and faster decline of GFR precede the development of microalbuminuria in type 1 diabetes. These findings support the hypothesis that renal hypertrophy precedes hyperfiltration during the development of diabetic nephropathy.

11C-Choline PET/CT Predicts Prostate Cancer–Specific Survival in Patients with Biochemical Failure During Androgen-Deprivation Therapy

Several studies have shown that 11C-choline PET/CT may be useful for restaging prostate cancer (PCa) patients with biochemical failure after radical prostatectomy. However, validation of 11C-choline PET/CT findings scarcely relied on histologic findings, and prognostic implications of 11C-choline PET/CT are currently unknown. The aim of this study was to assess whether 11C-choline PET/CT predicts survival in PCa patients. Methods: This retrospective study included 195 PCa patients treated with radical prostatectomy who underwent 11C-choline PET/CT from December 1, 2004, to July 31, 2007, due to biochemical failure (prostate-specific antigen > 0.2 mg/mL) during androgen-deprivation therapy. PCa-specific survival was computed as the interval from radical prostatectomy to PCa-specific death. Results: The median interval after radical prostatectomy was 8.9 y (95% confidence interval [CI], 1.7–18.9 y). The median follow-up after 11C-choline PET/CT was 4.5 y (95% CI, 0.4–8.5 y). 11C-choline PET/CT results were positive in 57% of patients. The median PCa-specific survival was 16.4 y (95% CI, 14.0–18.8 y) in patients with negative 11C-choline PET/CT results and 11.2 y (95% CI, 9.8–12.6 y) in patients with positive 11C-choline PET/CT results (log-rank: χ2 = 19.3, P < 0001). At multivariate analysis, statistical significance was obtained for 11C-choline PET/CT (hazard ratio, 2.53; 95% CI, 1.41–4.53; P = 0.002), prostate-specific antigen (hazard ratio, 1.03; 95% CI, 1.00–1.05; P = 0.037), and Gleason score (>7: hazard ratio, 2.49; 95% CI, 1.25–4.95; P = 0.009). Patients with pathologic 11C-choline uptake in the prostatic bed or in pelvic or retroperitoneal lymph nodes had longer PCa-specific survival (median, 12.1 y; 95% CI, 10.5–13.7 y) in comparison to patients with pathologic tracer uptake in the skeleton (median, 9.9 y; 95% CI, 6.8–13.1 y) (log-rank: χ2 = 6.5, P = 0.010). Two internally validated nomograms predicted 10- and 15-y PCa-specific survival probability with an accuracy of 76% and 74%, respectively. In an ancillary analysis, we also showed that 11C-choline PET/CT predicts PCa-specific survival after PET/CT, with similar statistical power. Conclusion: 11C-choline PET/CT predicts PCa-specific survival in PCa patients treated with radical prostatectomy who develop biochemical failure during androgen-deprivation therapy. If independent or multicenter confirmation of these findings is obtained, 11C-choline PET/CT might be more widely used in the follow-up of PCa patients for tailoring salvage therapy.

[11C]Choline Positron Emission Tomography/Computerized Tomography to Restage Prostate Cancer Cases With Biochemical Failure After Radical Prostatectomy and No Disease Evidence on Conventional Imaging

PURPOSE We assessed the value of [11C]choline positron emission tomography/computerized tomography in patients with prostate cancer in whom biochemical failure developed after radical prostatectomy but who showed no disease evidence on conventional imaging. MATERIALS AND METHODS Considered for this study were 2,124 patients treated with radical prostatectomy who underwent [11C]choline positron emission tomography/computerized tomography to restage disease between December 2004 and January 2007. Study inclusion criteria were 1) previous radical prostatectomy and pelvic lymph node dissection, 2) increasing prostate specific antigen beyond 0.2 ng/ml after radical prostatectomy, 3) no lymph node disease at radical prostatectomy, 4) no evidence of metastatic disease on conventional imaging, 5) no androgen deprivation therapy and 6) no adjuvant or salvage radiotherapy. These criteria were satisfied in 109 of the 2,124 patients (5%). RESULTS Median prostate specific antigen at imaging was 0.81 ng/ml (range 0.22 to 16.76 ml). Imaging suggested local recurrence in 4 patients (4%) and pelvic lymph node disease in 8 (7%). Scans were positive in 5%, 15% and 28% of patients with prostate specific antigen less than 1, between 1 and 2, and greater than 2 ng/ml, respectively (p <0.05). Prostate specific antigen was the only significant predictor of tomography results (p <0.05). CONCLUSIONS Positron emission tomography/computerized tomography detected increased [11C]choline uptake, suggesting recurrent disease in 11% of patients with prostate cancer, increasing prostate specific antigen after radical prostatectomy and no evidence of disease on conventional imaging. This modality may be useful to restage disease but it cannot be used to guide therapy.

Validation of an optimized SPM procedure for FDG-PET in dementia diagnosis in a clinical setting

Diagnostic accuracy in FDG-PET imaging highly depends on the operating procedures. In this clinical study on dementia, we compared the diagnostic accuracy at a single-subject level of a) Clinical Scenarios, b) Standard FDG Images and c) Statistical Parametrical (SPM) Maps generated via a new optimized SPM procedure. We evaluated the added value of FDG-PET, either Standard FDG Images or SPM Maps, to Clinical Scenarios. In 88 patients with neurodegenerative diseases (Alzheimers Disease—AD, Frontotemporal Lobar Degeneration—FTLD, Dementia with Lewy bodies—DLB and Mild Cognitive Impairment—MCI), 9 neuroimaging experts made a forced diagnostic decision on the basis of the evaluation of the three types of information. There was also the possibility of a decision of normality on the FDG-PET images. The clinical diagnosis confirmed at a long-term follow-up was used as the gold standard. SPM Maps showed higher sensitivity and specificity (96% and 84%), and better diagnostic positive (6.8) and negative (0.05) likelihood ratios compared to Clinical Scenarios and Standard FDG Images. SPM Maps increased diagnostic accuracy for differential diagnosis (AD vs. FTD; beta 1.414, p = 0.019). The AUC of the ROC curve was 0.67 for SPM Maps, 0.57 for Clinical Scenarios and 0.50 for Standard FDG Images. In the MCI group, SPM Maps showed the highest predictive prognostic value (mean LOC = 2.46), by identifying either normal brain metabolism (exclusionary role) or hypometabolic patterns typical of different neurodegenerative conditions.

Detection and compensation of organ/lesion motion using 4D-PET/CT respiratory gated acquisition techniques

PURPOSE To describe the degradation effects produced by respiratory organ and lesion motion on PET/CT images and to define the role of respiratory gated (RG) 4D-PET/CT techniques to compensate for such effects. METHODS Based on the literature and on our own experience, technical recommendations and clinical indications for the use of RG 4D PET/CT have been outlined. RESULTS RG 4D-PET/CT techniques require a state of the art PET/CT scanner, a respiratory monitoring system and dedicated acquisition and processing protocols. Patient training is particularly important to obtain a regular breathing pattern. An adequate number of phases has to be selected to balance motion compensation and statistical noise. RG 4D PET/CT motion free images may be clinically useful for tumour tissue characterization, monitoring patient treatment and target definition in radiation therapy planning. CONCLUSIONS RG 4D PET/CT is a valuable tool to improve image quality and quantitative accuracy and to assess and measure organ and lesion motion for radiotherapy planning.

Clinical evidence on PET/CT for radiation therapy planning in prostate cancer

The present chapter is focused on the role of positron emission tomography/computed tomography (PET/CT) and [11C]-labelled Choline ([11C]Choline) for the management of prostate cancer patients for radiation therapy planning. Although still a matter of debate, PET/CT with [11C]Choline is not routinely recommended for selecting patients for prostate cancer primary radiation treatment. However, due to its high accuracy in detecting and localizing recurrences when a biochemical failure occurs, [11C]Choline PET/CT may play a role in the re-staging phase to distinguish patients with local versus distant relapse, thus influencing patient management (curative versus palliative therapy). Limited data are currently available on the role of [11C]Choline PET/CT in target volume selection and delineation. According to available literature, [11C]Choline PET/CT is not clinically recommendable to plan target volume both for primary prostate treatment and for local recurrence. Nevertheless, promising data suggested a potential role of [11C]Choline PET/CT as an image guide tool for the irradiation of prostate cancer relapse.

Prostate-specific antigen velocity versus prostate-specific antigen doubling time for prediction of 11C choline PET/CT in prostate cancer patients with biochemical failure after radical prostatectomy

Purpose: We previously showed that prostate-specific antigen (PSA) doubling time (PSADT) is a significant predictor of 11C choline positron emission tomography/computed tomography (PET/CT) findings in prostate cancer (PCa) patients. This study compared PSA velocity (PSAV) and PSADT to predict 11C choline PET/CT findings. Materials and Methods: PSAV and PSADT were retrospectively calculated in 170 PCa patients with biochemical failure after radical prostatectomy, who underwent 11C choline PET/CT for restaging of disease. Results: Median PSA was 1.25 ng/mL (range: 0.23–48.6 ng/mL), and median PSAV was 0.99 ng/mL/y (range: 0.11–98.9 ng/mL/y). Patients with positive 11C choline PET/CT (n = 75) had significantly (P < 0.05) higher PSAV than patients with negative 11C choline PET/CT (n = 95) (6.93 ± 13.08 vs. 1.23 ± 2.03 ng/mL/y). The percent of patients with positive 11C choline PET/CT was 21% for PSAV <1 ng/mL/y, 56% for PSAV between 1 and 2 ng/mL/y, and 76% for PSAV >2 ng/mL/y. The quality of fitting (r2) of PSA values according to the exponential function (PSADT) was significantly (P < 0.05) better than the quality of fitting according to the linear function (PSAV) in the entire sample and in all anatomic regions. At multivariate analysis, trigger PSA, PSADT but not PSAV obtained the statistical significance (P < 0.05). Conclusions: PSAV can be used to stratify the risk of positive 11C choline PET/CT in PCa patients with biochemical failure. Patients with PSAV >1 ng/mL/y should be selected to increase the positive detection rate of 11C choline PET/CT. The greater statistical power of PSADT compared with PSAV could be related to the better capability of fitting time-dependent changes in PSA values, thereby better reflecting the natural growth of recurrent PCa.