Osman Ratib

Design and performance evaluation of a whole-body Ingenuity TF PET–MRI system

The Ingenuity TF PET-MRI is a newly released whole-body hybrid PET-MR imaging system with a Philips time-of-flight GEMINI TF PET and Achieva 3T X-series MRI system. Compared to PET-CT, modifications to the positron emission tomography (PET) gantry were made to avoid mutual system interference and deliver uncompromising performance which is equivalent to the standalone systems. The PET gantry was redesigned to introduce magnetic shielding for the photomultiplier tubes (PMTs). Stringent electromagnetic noise requirements of the MR system necessitated the removal of PET gantry electronics to be housed in the PET-MR equipment room. We report the standard NEMA measurements for the PET scanner. PET imaging and performance measurements were done at Geneva University Hospital as described in the NEMA Standards NU 2-2007 manual. The scatter fraction (SF) and noise equivalent count rate (NECR) measurements with the NEMA cylinder (20 cm diameter) were repeated for two larger cylinders (27 cm and 35 cm diameter), which better represent average and heavy patients. A NEMA/IEC torso phantom was used for overall assessment of image quality. The transverse and axial resolution near the center was 4.7 mm. Timing and energy resolution of the PET-MR system were measured to be 525 ps and 12%, respectively. The results were comparable to PET-CT systems demonstrating that the effect of design modifications required on the PET system to remove the harmful effect of the magnetic field on the PMTs was negligible. The absolute sensitivity of this scanner was 7.0 cps kBq(-1), whereas SF was 26%. NECR measurements performed with cylinders having three different diameters, and image quality measurements performed with IEC phantom yielded excellent results. The Ingenuity TF PET-MRI represents the first commercial whole-body hybrid PET-MRI system. The performance of the PET subsystem was comparable to the GEMINI TF PET-CT system using phantom and patient studies. It is conceived that advantages of hybrid PET-MRI will become more evident in the near future.

Assessment of various strategies for 18F-FET PET-guided delineation of target volumes in high-grade glioma patients

PurposeThe purpose of the study is to assess the contribution of 18F-fluoro-ethyl-tyrosine (18F-FET) positron emission tomography (PET) in the delineation of gross tumor volume (GTV) in patients with high-grade gliomas compared with magnetic resonance imaging (MRI) alone.Materials and methodsThe study population consisted of 18 patients with high-grade gliomas. Seven image segmentation techniques were used to delineate 18F-FET PET GTVs, and the results were compared to the manual MRI-derived GTV (GTVMRI). PET image segmentation techniques included manual delineation of contours (GTVman), a 2.5 standardized uptake value (SUV) cutoff (GTV2.5), a fixed threshold of 40% and 50% of the maximum signal intensity (GTV40% and GTV50%), signal-to-background ratio (SBR)-based adaptive thresholding (GTVSBR), gradient find (GTVGF), and region growing (GTVRG). Overlap analysis was also conducted to assess geographic mismatch between the GTVs delineated using the different techniques.ResultsContours defined using GTV2.5 failed to provide successful delineation technically in three patients (18% of cases) as SUVmax < 2.5 and clinically in 14 patients (78% of cases). Overall, the majority of GTVs defined on PET-based techniques were usually smaller than GTVMRI (67% of cases). Yet, PET detected frequently tumors that are not visible on MRI and added substantially tumor extension outside the GTVMRI in six patients (33% of cases).ConclusionsThe selection of the most appropriate 18F-FET PET-based segmentation algorithm is crucial, since it impacts both the volume and shape of the resulting GTV. The 2.5 SUV isocontour and GF segmentation techniques performed poorly and should not be used for GTV delineation. With adequate setting, the SBR-based PET technique may add considerably to conventional MRI-guided GTV delineation.

[(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma.

BackgroundTo compare morphological gross tumor volumes (GTVs), defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of 18F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning.MethodsNineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV ∪ BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed.ResultsInterrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (p = 0.9), CTVs (mean 57.8 ± 30.4 cm3) were significantly larger than BTVs (mean 42.1 ± 24.4 cm3; p < 0.01) or GTVs (mean 38.7 ± 25.7 cm3; p < 0.01). In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended ≥ 10 and 20 mm from the margin of the gadolinium enhancement.ConclusionUsing FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients.

Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases.

Abstract Background. Substantial survival may be observed with oligometastatic prostate cancer. Combining androgen deprivation (AD) and high-dose external beam radiotherapy (RT) to isolated regional or distant lesions may be proposed for these patients and the outcome of this strategy is the purpose of the present report. Material and methods. From 2003 to 2010, 50 prostate cancer patients were diagnosed with synchronous (n = 7) or metachronous (n = 43) oligometastases (OM). Among the relapsing patients, the recurrence occurred after radical prostatectomy in 33 patients and curative RT (± AD) in 10 patients. The median age at diagnosis was 63 years (range, 48–82). All patients underwent a bone scan and 18F-choline or 11C-acetate PET-CT at the time of diagnosis or relapse, showing regional and/or distant nodal and bone and/or visceral metastases in 33 and 17 patients, respectively. The median delivered effective dose was 64 Gy. All but one patient received neo-adjuvant and concomitant AD. Results. After a median follow-up of 31 months (range, 9–89) the three-year biochemical relapse-free survival (bRFS), clinical failure-free survival, and overall survival rates were 54.5%, 58.6% and 92%, respectively. No grade 3 toxicity was observed. Improved bRFS was found to be significantly associated with the number of OM. The three-year bRFS was 66.5% versus 36.4% for patients with 1 and > 1 OMs (p = 0.031). A normalised total dose (NTD in 2 Gy/fraction, alpha/beta = 2 Gy) above 64 Gy was also correlated with a better three-year bRFS compared to lower doses: 65% vs. 41.8%, respectively (p = 0.005). On multivariate analysis, only the NTD > 64 Gy retained statistical significance (HR: 0.37, 95% CI 0.15–0.93). Conclusion. Oligometastatic patients may be successfully treated with short AD and high-dose irradiation to the metastatic lesions. High dose improves bRFS. Such a treatment strategy may hypothetically succeed to prolong the failure-free interval between two consecutive AD courses.

Augmented reality and image overlay navigation with OsiriX in laparoscopic and robotic surgery: not only a matter of fashion

BackgroundNew technologies can considerably improve preoperative planning, enhance the surgeon’s skill and simplify the approach to complex procedures. Augmented reality techniques, robot assisted operations and computer assisted navigation tools will become increasingly important in surgery and in residents’ education.MethodsWe obtained 3D reconstructions from simple spiral computed tomography (CT) slides using OsiriX, an open source processing software package dedicated to DICOM images. These images were then projected on the patients body with a beamer fixed to the operating table to enhance spatial perception during surgical intervention (augmented reality).ResultsChanging a windows deepness level allowed the surgeon to navigate through the patients anatomy, highlighting regions of interest and marked pathologies. We used image overlay navigation for laparoscopic operations such cholecystectomy, abdominal exploration, distal pancreas resection and robotic liver resection.ConclusionsAugmented reality techniques will transform the behaviour of surgeons, making surgical interventions easier, faster and probably safer. These new techniques will also renew methods of surgical teaching, facilitating transmission of knowledge and skill to young surgeons.

Elevated endocannabinoid plasma levels are associated with coronary circulatory dysfunction in obesity.

AIMS Aim of this study was to evaluate a possible association between endocannabinoid (EC) plasma levels, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and coronary circulatory function in obesity. METHODS AND RESULTS Myocardial blood flow (MBF) responses to cold pressor test (CPT) and during pharmacological vasodilation with dipyridamole were measured with (13)N-ammonia PET/CT. Study participants (n = 77) were divided into three groups based on their body mass index (BMI, kg/m(2)): control group 20 ≤ BMI <25 (n = 21); overweight group, 25 ≤ BMI <30 (n = 26); and obese group, BMI ≥ 30 (n = 30). Anandamide plasma levels, but not 2-AG plasma levels, were significantly elevated in obesity as compared with controls, respectively [0.68 (0.53, 0.78) vs. 0.56 (0.47, 0.66) ng/mL, P = 0.020, and 2.2 (1.21, 4.59) vs. 2.0 (0.80, 5.90) ng/mL, P = 0.806)]. The endothelium-related change in MBF during CPT from rest (ΔMBF) progressively declined in overweight and obese when compared with control group [0.21 (0.10, 0.27) and 0.09 (-0.01, 0.15) vs. 0.26 (0.23, 0.39) mL/g/min; P = 0.010 and P = 0.0001, respectively). Compared with controls, hyperaemic MBFs were significantly lower in overweight and obese individuals [2.39 (1.97, 2.62) vs. 1.98 (1.69, 2.26) and 2.10 (1.76, 2.36); P = 0.007 and P = 0.042, respectively)]. In obese individuals, AEA and 2-AG plasma levels were inversely correlated with ΔMBF to CPT (r = -0.37, P = 0.046 and r = -0.48, P = 0.008) and hyperaemic MBFs (r = -0.38, P = 0.052 and r = -0.45, P = 0.017), respectively. CONCLUSIONS Increased EC plasma levels of AEA and 2-AG are associated with coronary circulatory dysfunction in obese individuals. This observation might suggest increases in EC plasma levels as a novel endogenous cardiovascular risk factor in obesity, but needing further investigations.

Clinical applications of hybrid PET/MRI in neuroimaging.

Purpose We tested the performance and clinical applicability of combined protocols for brain imaging studies acquired on a new whole-body hybrid PET/MR scanner. Patients and Methods Fifteen patients [6 male and 9 female patients; mean (SD) age, 51 (30) y; range, 6–89 y] were scanned on a Philips Ingenuity TF PET/MR. Standard imaging protocols of both modalities were combined, using a “head coil” and contrast-enhanced fully diagnostic MR protocols. Attenuation correction of the PET images was performed using tissue segmentation of the MR image and incorporation of attenuation templates measured for coils and table. The clinical indications evaluated are as follows: patients with cognitive disturbance of suspected neurodegenerative origin, presurgical evaluation of drug-refractory epilepsy, and brain tumor staging. For the first 2 indications, FDG PET imaging was performed, whereas for the last, fluoroethyltyrosine, an amino acid tracer, was used. Results In all cases (4 patients with neurodegenerative disease, 6 patients with epilepsy, and 5 patients with high-grade tumor), we obtained full diagnostic quality of both modalities and the total duration of the examination remained within a tolerable range (<2 hours). Twelve subjects had pathological findings: 11 of which were confirmed by clinical follow-up as true positive and 1 was confirmed as a false-positive result. For the 3 normal studies, the clinical follow-up confirmed the imaging findings as true-negative. Conclusions Acquiring both PET and MR in a single session on a hybrid system minimized patient discomfort while maximizing clinical information and optimizing registration of both modalities. In addition, in comparison to PET/CT, the effective dose (related to CT) was reduced, and this is particularly beneficial in the pediatric population.

Detection and quantification of focal uptake in head and neck tumours: 18 F-FDG PET/MR versus PET/CT

PurposeOur objectives were to assess the quality of PET images and coregistered anatomic images obtained with PET/MR, to evaluate the detection of focal uptake and SUV, and to compare these findings with those of PET/CT in patients with head and neck tumours.MethodsThe study group comprised 32 consecutive patients with malignant head and neck tumours who underwent whole-body 18F-FDG PET/MR and PET/CT. PET images were reconstructed using the attenuation correction sequence for PET/MR and CT for PET/CT. Two experienced observers evaluated the anonymized data. They evaluated image and fusion quality, lesion conspicuity, anatomic location, number and size of categorized (benign versus assumed malignant) lesions with focal uptake. Region of interest (ROI) analysis was performed to determine SUVs of lesions and organs for both modalities. Statistical analysis considered data clustering due to multiple lesions per patient.ResultsPET/MR coregistration and image fusion was feasible in all patients. The analysis included 66 malignant lesions (tumours, metastatic lymph nodes and distant metastases), 136 benign lesions and 470 organ ROIs. There was no statistically significant difference between PET/MR and PET/CT regarding rating scores for image quality, fusion quality, lesion conspicuity or anatomic location, number of detected lesions and number of patients with and without malignant lesions. A high correlation was observed for SUVmean and SUVmax measured on PET/MR and PET/CT for malignant lesions, benign lesions and organs (ρ = 0.787 to 0.877, p < 0.001). SUVmean and SUVmax measured on PET/MR were significantly lower than on PET/CT for malignant tumours, metastatic neck nodes, benign lesions, bone marrow, and liver (p < 0.05). The main factor affecting the difference between SUVs in malignant lesions was tumour size (p < 0.01).ConclusionIn patients with head and neck tumours, PET/MR showed equivalent performance to PET/CT in terms of qualitative results. Comparison of SUVs revealed an excellent correlation for measurements on both modalities, but underestimation of SUVs measured on PET/MR as compared to PET/CT.

FDG-PET/CT pitfalls in oncological head and neck imaging

ObjectivesPositron emission tomography-computed tomography (PET/CT) with fluorine-18-fluorodeoxy-D-glucose (FDG) has evolved from a research modality to an invaluable tool in head and neck cancer imaging. However, interpretation of FDG PET/CT studies may be difficult due to the inherently complex anatomical landmarks, certain physiological variants and unusual patterns of high FDG uptake in the head and neck. The purpose of this article is to provide a comprehensive approach to key imaging features and interpretation pitfalls of FDG-PET/CT of the head and neck and how to avoid them.MethodsWe review the pathophysiological mechanisms leading to potentially false-positive and false-negative assessments, and we discuss the complementary use of high-resolution contrast-enhanced head and neck PET/CT (HR HN PET/CT) and additional cross-sectional imaging techniques, including ultrasound (US) and magnetic resonance imaging (MRI).ResultsThe commonly encountered false-positive PET/CT interpretation pitfalls are due to high FDG uptake by physiological causes, benign thyroid nodules, unilateral cranial nerve palsy and increased FDG uptake due to inflammation, recent chemoradiotherapy and surgery. False-negative findings are caused by lesion vicinity to structures with high glucose metabolism, obscuration of FDG uptake by dental hardware, inadequate PET scanner resolution and inherent low FDG-avidity of some tumours.ConclusionsThe interpreting physician must be aware of these unusual patterns of FDG uptake, as well as limitations of PET/CT as a modality, in order to avoid overdiagnosis of benign conditions as malignancy, as well as missing out on actual pathology.Teaching points• Knowledge of key imaging features of physiological and non-physiological FDG uptake is essential for the interpretation of head and neck PET/CT studies.• Precise anatomical evaluation and correlation with contrast-enhanced CT, US or MRI avoid PET/CT misinterpretation.• Awareness of unusual FDG uptake patterns avoids overdiagnosis of benign conditions as malignancy.

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers

The diagnosis of Alzheimers disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimers disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimers disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.