Early monitoring of external radiation therapy by [18F]-fluoromethylcholine positron emission tomography and 3-T proton magnetic resonance spectroscopy: an experimental study in a rodent rhabdomyosarcoma model.

PURPOSE: To assess early radiation therapy (RT)-induced variations in total choline (tCho) concentration measured by proton magnetic resonance spectroscopy (H-MRS) and in (18)F-labelled fluoromethylcholine (FCH) uptake measured by PET in a rodent tumour model. METHODS: Nine rats bearing syngenic rhabdomyosarcoma grafts in both thighs were irradiated (13 Gy, one fraction). H-MRS data and FCH-PET were acquired in the same imaging session prior to and 3, 9 and 16 days after external RT. Total choline concentration was expressed in arbitrary units as the area under the curve of the 3.2-ppm peak on H-MR spectra. FCH uptake was expressed as maximum standardized uptake value (SUV(max)) and as the % of injected dose per gram (%ID/g) after precise tumour delineation on hybrid PET-MR images. Pre- and post-RT data were compared using the Student's paired t test, and results were expressed as mean+/-S.D. RESULTS: Seventeen tumours were available for analysis. A mean drop in choline concentration of 45% was observed 3 days after irradiation (P<.001), whereas a concomitant mean increase in SUV(max) of 41% was observed (P=.006). Choline concentration reincreased on later time points. CONCLUSIONS: Opposite trend between increased FCH uptake and decreased tCho peak was observed at 3 days. Later (9 and 16 days), uptake remained stable and tCho peak reincreased.

MRI-based attenuation correction for PET/MRI using ultrashort echo time sequences.

UNLABELLED: One of the challenges in PET/MRI is the derivation of an attenuation map to correct the PET image for attenuation. Different methods have been suggested for deriving the attenuation map from an MR image. Because the low signal intensity of cortical bone on images acquired with conventional MRI sequences makes it difficult to detect this tissue type, these methods rely on some sort of anatomic precondition to predict the attenuation map, raising the question of whether these methods will be usable in the clinic when patients may exhibit anatomic abnormalities. METHODS: We propose the use of the transverse relaxation rate, derived from images acquired with an ultrashort echo time sequence to classify the voxels into 1 of 3 tissue classes (bone, soft tissue, or air), without making any assumptions on patient anatomy. Each voxel is assigned a linear attenuation coefficient corresponding to its tissue class. A reference CT scan is used to determine the voxel-by-voxel accuracy of the proposed method. The overall accuracy of the MRI-based attenuation correction is evaluated using a method that takes into account the nonlocal effects of attenuation correction. RESULTS: As a proof of concept, the head of a pig was used as a phantom for imaging. The new method yielded a correct tissue classification in 90% of the voxels. Five human brain PET/CT and MRI datasets were also processed, yielding slightly worse voxel-by-voxel performance, compared to a CT-derived attenuation map. The PET datasets were reconstructed using the segmented MRI attenuation map derived with the new method, and the resulting images were compared with segmented CT-based attenuation correction. An average error of around 5% was found in the brain. CONCLUSION: The feasibility of using the transverse relaxation rate map derived from ultrashort echo time MR images for the estimation of the attenuation map was shown on phantom and clinical brain data. The results indicate that the new method, compared with CT-based attenuation correction, yields clinically acceptable errors. The proposed method does not make any assumptions about patient anatomy and could therefore also be used in cases in which anatomic abnormalities are present.

Lung cancer: Morphological and functional approach to screening, staging and treatment planning.

Lung cancer is a major problem in public health and constitutes the leading cause of cancer-related mortality in the world. Lung cancer screening with low-dose computed tomography is promising but needs to overcome many difficulties, such as the large number of incidentally discovered nodules, the radiation dose delivered to the patient during a whole screening program and its cost. The ultimate target point represented by the reduction of lung cancer-related mortality needs to be proved in large, well-designed, randomized, multicenter, prospective trials. Lung cancer staging by morphological tools seems to be limited owing to the presence of metastases in normal-sized lymph nodes. In this context, multidetector computed tomography cannot be used alone but is useful in conjunction with molecular imaging and MRI. Today, flurodeoxglucose PET-CT appears to be the most accurate method for lung cancer staging and may prevent unnecessary thoracotomies. For treatment planning, flurodeoxglucose PET-CT is playing an increasing role in radiotherapy planning at the target selection and definition steps.

Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient management in patients with head and neck squamous cell carcinoma: a multicenter prospective study.

PURPOSE To address the impact of positron emission tomography with [(18)F]fluorodeoxyglucose (PET-FDG) on the initial staging and management of patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS This multicenter, prospective study included 233 patients with newly diagnosed and untreated HNSCC. TNM stage and therapeutic decision were first determined based on the conventional work-up (including physical examination, computed tomography [CT]/magnetic resonance imaging of the head and neck region, and thoracic CT) and sealed in envelope 1. Whole-body PET-FDG was then performed, and subsequent TNM stage and therapeutic decision were written in envelope 2. Changes in TNM stages and in patient management as a result of PET-FDG imaging were recorded. Clinical outcome and histopathology were used as gold standards to validate the TNM stage. Conventional and PET stages were compared using the McNemar test. Results Conventional and PET stage were discordant in 100 (43%) of 233 patients. PET proved to be accurate in 47 patients and inaccurate in 13 patients. TNM status was left unconfirmed in 40 patients because no therapeutic change was expected from the stage difference. Conventional + PET TNM classification (envelope 2) was significantly more accurate than conventional classification (envelope 1; P < .0001, McNemar test). PET-FDG altered the therapeutic plan in 32 (13.7%) of 233 patients. CONCLUSION Adding whole-body PET-FDG to the pretherapeutic conventional staging of HNSCC improved the TNM classification of the disease and altered the management of 13.7% of patients. These findings support the implementation of PET-FDG in the routine imaging work-up of HNSCC.

Cost-effectiveness analysis of FDG PET-CT in the management of pulmonary metastases from malignant melanoma.

OBJECTIVES: Most guidelines consider FDG PET-CT to detect occult extra-pulmonary disease prior to lung metastasectomy. A cost-effectiveness analysis, using a Markov model over a 10 year period, was performed to compare two different surveillance programs, either PET-CT or whole-body CT, in patients with suspected pulmonary metastasised melanoma. METHODS: Data from published studies provided probabilities for the model. Complication and care costs were obtained from standardised administrative databases from 19 hospitals identified by DRG codes (reported in 2009 Euros). For the cost calculation of PET-CT we performed a microcosting analysis. All costs and benefits were yearly discounted at respectively 3% and 1.5%. Outcomes included life-months gained (LMG) and the number of futile surgeries avoided. Cost-effectiveness ratios were in Euros per LMG. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters. RESULTS: The PET-CT strategy provided 86.29 LMG (95% CI: 81.50-90.88 LMG) at a discounted cost of euro3,974 (95% CI: euro1,339-12,303), while the conventional strategy provided 86.08 LMG (95% CI: 81.37-90.68 LMG) at a discounted cost of euro5,022 (95% CI: euro1,378-16,018). This PET-CT strategy resulted in a net saving of euro1,048 with a gain of 0.2 LMG. Based on PET-CT findings, 20% of futile surgeries could be avoided. CONCLUSION: Integrating PET-CT in the management of patients with high risk MM appears to be less costly and more accurate by avoiding futile thoracotomies in one of five patients as well as by providing a small survival benefit at 10 years.

Optimization of time-of-flight reconstruction on Philips GEMINI TF.

PURPOSE: The aim of this study is to optimize different parameters in the time-of-flight (TOF) reconstruction for the Philips GEMINI TF. The use of TOF in iterative reconstruction introduces additional variables to be optimized compared to conventional PET reconstruction. The different parameters studied are the TOF kernel width, the kernel truncation (used to reduce reconstruction time) and the scatter correction method. METHODS: These parameters are optimized using measured phantom studies. All phantom studies were acquired with a very high number of counts to limit the effects of noise. A high number of iterations (33 subsets and 3 iterations) was used to reach convergence. The figures of merit are the uniformity in the background, the cold spot recovery and the hot spot contrast. As reference results we used the non-TOF reconstruction of the same data sets. RESULTS: It is shown that contrast recovery loss can only be avoided if the kernel is extended to more than 3 standard deviations. To obtain uniform reconstructions the recommended scatter correction is TOF single scatter simulation (SSS). This also leads to improved cold spot recovery and hot spot contrast. While the daily measurements of the system show a timing resolution in the range of 590­600 ps, the optimal reconstructions are obtained with a TOF kernel full-width at half-maximum (FWHM) of 650­700 ps. The optimal kernel width seems to be less critical for the recovered contrast but has an important effect on the background uniformity. Using smaller or wider kernels results in a less uniform background and reduced hot and cold contrast recovery. CONCLUSION: The different parameters studied have a large effect on the quantitative accuracy of the reconstructed images. The optimal settings from this study can be used as a guideline to make an objective comparison of the gains obtained with TOF PET versus PET reconstruction.

Role of PET in the initial staging of cutaneous malignant melanoma: systematic review.

PURPOSE: To calculate summary estimates of the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging in the initial staging of cutaneous malignant melanoma (CMM), following the new American Joint Committee on Cancer (AJCC) staging classification on per-patient and per-lesion bases. MATERIALS AND METHODS: MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews databases, and reference lists of reviews and included papers were searched, without any language restrictions, for relevant articles published before March 2007. Two reviewers independently assessed study eligibility and methodologic quality by using the quality assessment of diagnostic accuracy studies checklist. A pooled random effect was estimated and a fixed coefficient regression model was used to explore the existing heterogeneity. RESULTS: Twenty-eight studies involving 2905 patients met the inclusion criteria. The pooled estimates of FDG PET for the detection of metastasis in the initial staging of CMM were sensitivity, 83% (95% confidence interval [CI]: 81%, 84%); specificity, 85% (95% CI: 83%, 87%); positive likelihood ratio (LR), 4.56 (95% CI: 3.12, 6.64); negative LR, 0.27 (95% CI: 0.18, 0.40); and diagnostic odds ratio, 19.8 (95% CI: 10.8, 36.4). Results from eight studies suggested that FDG PET was associated with 33% disease management changes (range, 15%-64%). CONCLUSION: There is good preliminary evidence that FDG PET is useful for the initial staging of patients with CMM, especially as adjunctive role in AJCC stages III and IV, to help detect deep soft-tissue, lymph node, and visceral metastases. FDG PET-computed tomographic imaging seemed to be more precise than PET alone, as suggested by four eligible studies. Further evaluation by using a well-designed prospective study, with clinical outcome-focused measures and cost effectiveness analysis, is needed to clarify the appropriate role of FDG PET in CMM staging. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/249/3/836/DC1.

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

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

Prognostic value of FDG uptake in early stage non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) has a poor prognosis even for early stages of the disease (stage I and II). We studied the prognostic value of PET FDG in patients with completely resected stage I and II NSCLC. METHODS: Retrospective study of 96 patients with NSCLC whose staging included 18F-FDG PET (fluoro deoxy glucose positron emission tomography). Histopathological stage was either stage I (75) or stage II (n=21). FDG uptake was measured as maximal standardized uptake value for body weight (SUVmax). Mean follow-up was 45+/-30 months (1-142 months). Overall and cancer-free survival rates were recorded. RESULTS: SUVmax were higher for stage II than for stage I (10.5+/-4.5 vs 8.5+/-5, p=0.04). Mean tumor volumes were equivalent for both stages (33 cm3, p=0.18), excluding a partial volume effect. The median SUVmax in the whole study population was 7.8. The median survival was significantly longer in patients with a lower (SUVmax7.8 (p=0.001). For stage II tumors (n=21), no statistical difference was observed: 72 months vs 40 months for SUVmax7.8, respectively (p=0.11), although there was a clear trend towards reduced survival for highly metabolic tumors. Disease-free survival was also significantly better for lower metabolic tumors: 96.1 months vs 87.7 months (p=0.01). CONCLUSION: High FDG uptake is associated with reduced overall survival and disease-free survival of patients with completely resected stage I-II NSCLC. Whether patients with highly metabolic tumors should undergo a closer postoperative surveillance or adjuvant chemotherapy has to be addressed in a properly designed prospective trial.

FDG-PET and PET/CT in Colorectal Cancer.

This article reviews the current use of FDG PET/CT for assessment of colorectal cancer. Initial diagnosis and staging are covered, as well as detection and staging of tumor recurrence. The current place of FDG PET/CT is discussed in light of recently published studies. Besides the well-established use of PET for detecting and staging colorectal cancer relapse, potential new indications, such as initial pretherapeutic staging, as well as risk stratification are discussed.

Adaptive biological image-guided IMRT with anatomic and functional imaging in pharyngo-laryngeal tumors: impact on target volume delineation and dose distribution using helical tomotherapy.

BACKGROUND AND PURPOSE: Adaptive image-guided IMRT appears to be a promising approach for dose escalation in pharyngo-laryngeal tumors. In this framework, we assessed in a proof of concept study the impact of anatomic and functional imaging modalities acquired prior and during radiotherapy on the target volume delineation and the dose distribution using helical tomotherapy. MATERIALS AND METHODS: Ten patients with pharyngo-laryngeal squamous cell carcinoma were treated by concomitant chemo-radiation delivered in 7 weeks. CT, T2-MRI, fat suppressed T2-MRI, and static and dynamic FDG-PET were acquired for each patient before the start of treatment and during radiotherapy, after mean prescribed doses of 14, 25, 35 and 45 Gy. GTVs were manually delineated on CT and MRI images while PET images were automatically segmented by means of a gradient-based method. From these volumes, CTVs and PTVs were derived using consistent guidelines. Simultaneous integrated boost IMRT planning was performed using helical tomotherapy. RESULTS: GTVs significantly decreased throughout the course of RT for all imaging modalities (p<0.001). Clinically non-significant differences and high correlations were found between GTVs delineated on CT and MRI, irrespective of the sequence used. By contrast, FDG-PET-based GTVs segmented from pre- and per-treatment images were significantly smaller compared to anatomical imaging modalities, without any difference existing between static and dynamic acquisition. These differences in GTVs translated into parallel reductions of both prophylactic and therapeutic CTVs and PTVs. Resulting FDG-PET-based and adaptive IMRT planning reduced the irradiated volumes by 15-40% compared to pre-treatment CT planning (V(90), V(95) and V(100)), but did marginally impact on doses to the OAR such as the spinal cord and the parotid glands. CONCLUSIONS: Adaptive IMRT with FDG-PET images has a significant impact on the delineation of TVs and on the dose distribution in pharyngo-laryngeal tumors. Such an approach might thus be considered for dose escalation strategies.

Positron emission tomography-guided, focal-dose escalation using intensity-modulated radiotherapy for head and neck cancer.

PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. METHODS AND MATERIALS: A Phase I clinical trial was designed to escalate the dose limited to the [(18)-F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy. RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.

A gradient-based method for segmenting FDG-PET images: methodology and validation.

PURPOSE: A new gradient-based method for segmenting FDG-PET images is described and validated. METHODS: The proposed method relies on the watershed transform and hierarchical cluster analysis. To allow a better estimation of the gradient intensity, iteratively reconstructed images were first denoised and deblurred with an edge-preserving filter and a constrained iterative deconvolution algorithm. Validation was first performed on computer-generated 3D phantoms containing spheres, then on a real cylindrical Lucite phantom containing spheres of different volumes ranging from 2.1 to 92.9 ml. Moreover, laryngeal tumours from seven patients were segmented on PET images acquired before laryngectomy by the gradient-based method and the thresholding method based on the source-to-background ratio developed by Daisne (Radiother Oncol 2003;69:247-50). For the spheres, the calculated volumes and radii were compared with the known values; for laryngeal tumours, the volumes were compared with the macroscopic specimens. Volume mismatches were also analysed. RESULTS: On computer-generated phantoms, the deconvolution algorithm decreased the mis-estimate of volumes and radii. For the Lucite phantom, the gradient-based method led to a slight underestimation of sphere volumes (by 10-20%), corresponding to negligible radius differences (0.5-1.1 mm); for laryngeal tumours, the segmented volumes by the gradient-based method agreed with those delineated on the macroscopic specimens, whereas the threshold-based method overestimated the true volume by 68% (p=0.014). Lastly, macroscopic laryngeal specimens were totally encompassed by neither the threshold-based nor the gradient-based volumes. CONCLUSION: The gradient-based segmentation method applied on denoised and deblurred images proved to be more accurate than the source-to-background ratio method.