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1.  Usefulness of Integrated PET/MRI in Head and Neck Cancer: A Preliminary Study 
Purpose
The new modality of an integrated positron emission tomography/magnetic resonance imaging (PET/MRI) has recently been introduced but not validated. Our objective was to evaluate clinical performance of 18F-fluoro-2-deoxyglucose (18F-FDG) PET/MRI in patients with head and neck cancer.
Methods
This retrospective study was conducted between January 2013 and February 2013. Ten patients (eight men, two women; mean age, 61.4 ± 13.4 years) with histologically proven head and neck tumors were enrolled. Whole-body PET/MRI and regional positron emission tomography (PET) with dedicated MRI were sequentially obtained. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume, total lesion glycolysis and contrast enhancement were analyzed. A total of ten whole-body positron emission tomography (PET), ten regional positron emission tomography (PET), ten dedicated MRI and ten regional PET/gadolinium-enhanced T1-weighted (Gd)-MRI images were analyzed for initial staging. Two nuclear medicine physicians analyzed positron emission tomography (PET) and PET/MRI with a consensus. One radiologist analyzed dedicated MRI. The primary lesions and number of metastatic lymph nodes analyzed from each image were compared.
Results
Eight patients were diagnosed with head and neck cancer (one tongue cancer, four tonsillar cancers, one nasopharyngeal cancer and two hypopharyngeal cancers) by histological diagnosis. Two benign tumors (pleomorphic adenoma and Warthin tumor) were diagnosed with surgical operation. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) attenuated by MRI showed good image quality for the lesion detection. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) detected ten primary sites and compensated for a missed lesion on dedicated MRI. A discordant number of suspicious lymph node metastases was noted according to the different images; 22, 16, 39 and 40 in the whole-body positron emission tomography (PET) only, dedicated MR, regional positron emission tomography (PET) only and regional PET/Gd-MRI, respectively. There was no distant metastasis based on analysis of whole-body positron emission tomography (PET) and whole-body PET/Dixon-volume interpolated breathhold examination (VIBE) MRI. Regional PET/Gd-MRI combined with whole-body PET/MRI modified staging in three patients. Lesions of primary tumor and suspicious metastasis were well detected on both value of SUVmax and visual analysis. The regional PET/Gd-MRI combined with whole-body PET/MRI showed convenient clinical staging performance compared with positron emission tomography (PET) and MRI alone.
Conclusion
In this preliminary study, PET attenuated by MRI showed good image quality to detect lesions. And whole-body PET/MRI as a single modality was feasible for staging in a clinical setting. Whole-body positron emission tomography (PET), regional positron emission tomography (PET), dedicated MRI and regional PET/Gd-MRI showed discordant results in lesion detection. These discordant results might be synergistic effect for accurate staging.
doi:10.1007/s13139-013-0252-2
PMCID: PMC4028474  PMID: 24900149
Head and neck cancer; Oncology; PET; MRI; Integrated PET/MRI
2.  Usefulness of Integrated PET/MRI in Head and Neck Cancer: A Preliminary Study 
Purpose
The new modality of an integrated positron emission tomography/magnetic resonance imaging (PET/MRI) has recently been introduced but not validated. Our objective was to evaluate clinical performance of 18F-fluoro-2-deoxyglucose (18F-FDG) PET/MRI in patients with head and neck cancer.
Methods
This retrospective study was conducted between January 2013 and February 2013. Ten patients (eight men, two women; mean age, 61.4 ± 13.4 years) with histologically proven head and neck tumors were enrolled. Whole-body PET/MRI and regional positron emission tomography (PET) with dedicated MRI were sequentially obtained. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume, total lesion glycolysis and contrast enhancement were analyzed. A total of ten whole-body positron emission tomography (PET), ten regional positron emission tomography (PET), ten dedicated MRI and ten regional PET/gadolinium-enhanced T1-weighted (Gd)-MRI images were analyzed for initial staging. Two nuclear medicine physicians analyzed positron emission tomography (PET) and PET/MRI with a consensus. One radiologist analyzed dedicated MRI. The primary lesions and number of metastatic lymph nodes analyzed from each image were compared.
Results
Eight patients were diagnosed with head and neck cancer (one tongue cancer, four tonsillar cancers, one nasopharyngeal cancer and two hypopharyngeal cancers) by histological diagnosis. Two benign tumors (pleomorphic adenoma and Warthin tumor) were diagnosed with surgical operation. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) attenuated by MRI showed good image quality for the lesion detection. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) detected ten primary sites and compensated for a missed lesion on dedicated MRI. A discordant number of suspicious lymph node metastases was noted according to the different images; 22, 16, 39 and 40 in the whole-body positron emission tomography (PET) only, dedicated MR, regional positron emission tomography (PET) only and regional PET/Gd-MRI, respectively. There was no distant metastasis based on analysis of whole-body positron emission tomography (PET) and whole-body PET/Dixon-volume interpolated breathhold examination (VIBE) MRI. Regional PET/Gd-MRI combined with whole-body PET/MRI modified staging in three patients. Lesions of primary tumor and suspicious metastasis were well detected on both value of SUVmax and visual analysis. The regional PET/Gd-MRI combined with whole-body PET/MRI showed convenient clinical staging performance compared with positron emission tomography (PET) and MRI alone.
Conclusion
In this preliminary study, PET attenuated by MRI showed good image quality to detect lesions. And whole-body PET/MRI as a single modality was feasible for staging in a clinical setting. Whole-body positron emission tomography (PET), regional positron emission tomography (PET), dedicated MRI and regional PET/Gd-MRI showed discordant results in lesion detection. These discordant results might be synergistic effect for accurate staging.
doi:10.1007/s13139-013-0252-2
PMCID: PMC4028474  PMID: 24900149
Head and neck cancer; Oncology; PET; MRI; Integrated PET/MRI
3.  On the Added Value of Baseline FDG-PET in Malignant Lymphoma 
Molecular Imaging and Biology  2009;12(2):225-232.
Purpose
The added value of baseline positron emission tomography (PET) scans in therapy evaluation in malignant lymphoma is unclear. In guidelines, baseline PET is recommended but not mandatory except in lymphoma types with variable fluoro-d-glucose uptake. The aim of the present study was to test the hypothesis that adding baseline PET information decreases false positive readings with posttreatment PET and improves observer agreement.
Methods
Forty-four patients (mean age 56 years, standard deviation 14) with malignant lymphoma were included. Two nuclear medicine physicians retrospectively and independently evaluated the posttreatment PET, 3 weeks later followed by paired reading of baseline and posttreatment PET. For each PET, 22 regions were classified as positive, negative, or equivocal, resulting in an overall PET score of positive, unclear, or negative. In case of discrepancies, consensus was reached.
Results
Addition of baseline to posttreatment PET evaluation affected the classification of metabolic response in 34% of malignant lymphoma patients treated with first-line chemotherapy. In one out of seven patients, addition of the baseline PET lead to opposite conclusions (95% confidence interval 4–14). False positivity was reduced by adding the baseline scan information, but the effect on false negativity was similar. In addition, the amount of unclear classifications halved after paired reading. Observer agreement did not improve upon adding the baseline PET data.
Conclusion
Without any other clinical information, pretreatment PET facilitates changes the interpretation of a posttreatment PET in a third of the patients, resulting in both upgrading and downgrading of the posttreatment situation of a malignant lymphoma patient. If these results are confirmed for PET–computed tomography systems, they favor the addition of baseline PET to the current work-up of patients with malignant lymphoma.
doi:10.1007/s11307-009-0259-3
PMCID: PMC2844531  PMID: 19809855
FDG PET; Malignant lymphoma; Therapy evaluation; Baseline PET; Hodgkin’s disease; Non-Hodgkin’s lymphoma
4.  Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer 
Frontiers in Oncology  2013;2:208.
The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated 18F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. 18F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. 18F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on 18F-FDG-PET scan when CT criteria for malignant involvement are not met. 18F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. 18F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. 18F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3–6 months, using 18F-FDG-PET to evaluate equivocal CT findings. As high 18F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, 18F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable 18F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.
doi:10.3389/fonc.2012.00208
PMCID: PMC3539654  PMID: 23316478
PET; non-small cell lung cancer; staging; response assessment; follow-up
5.  Positron Emission Tomography for the Assessment of Myocardial Viability 
Executive Summary
Objective
The objective was to update the 2001 systematic review conducted by the Institute For Clinical Evaluative Sciences (ICES) on the use of positron emission tomography (PET) in assessing myocardial viability. The update consisted of a review and analysis of the research evidence published since the 2001 ICES review to determine the effectiveness and cost-effectiveness of PET in detecting left ventricular (LV) viability and predicting patient outcomes after revascularization in comparison with other noninvasive techniques.
Background
Left Ventricular Viability
Heart failure is a complex syndrome that impairs the contractile ability of the heart to maintain adequate blood circulation, resulting in poor functional capacity and increased risk of morbidity and mortality. It is the leading cause of hospitalization in elderly Canadians. In more than two-thirds of cases, heart failure is secondary to coronary heart disease. It has been shown that dysfunctional myocardium resulting from coronary heart disease (CAD) may recover contractile function (i.e. considered viable). Dysfunctional but viable myocardium may have been stunned by a brief episode of ischemia, followed by restoration of perfusion, and may regain function spontaneously. It is believed that repetitive stunning results in hibernating myocardium that will only regain contractile function upon revascularization.
For people with CAD and severe LV dysfunction (left ventricular ejection fraction [LVEF] <35%) refractory to medical therapy, coronary artery bypass and heart transplantation are the only treatment options. The opportunity for a heart transplant is limited by scarcityof donor hearts. Coronary artery bypass in these patients is associated with high perioperative complications; however, there is evidence that revascularization in the presence of dysfunctional but viable myocardium is associated with survival benefits and lower rates of cardiac events. The assessment of left ventricular (LV) viability is, therefore, critical in deciding whether a patient with coronary artery disease and severe LV dysfunction should undergo revascularization, receive a heart transplant, or remain on medical therapy.
Assessment of Left Ventricular Viability
Techniques for assessing myocardial viability depend on the measurement of a specific characteristic of viable myocytes such as cell membrane integrity, preserved metabolism, mitochondria integrity, and preserved contractile reserve. In Ontario, single photon emission computed tomography (SPECT) using radioactive 201thallium is the most commonly used technique followed by dobutamine echocardiography. Newer techniques include SPECT using technetium tracers, cardiac magnetic resonance imaging, and PET, the subject of this review.
Positron Emission Tomography
PET is a nuclear imaging technique based on the metabolism of radioactive analogs of normal substrates such as glucose and water. The radiopharmaceutical used most frequently in myocardial viability assessment is F18 fluorodeoxyglucose (FDG), a glucose analog. The procedure involves the intravenous administration of FDG under controlled glycemic conditions, and imaging with a PET scanner. The images are reconstructed using computer software and analyzed visually or semi-quantitatively, often in conjunction with perfusion images. Dysfunctional but stunned myocardium is characterized by normal perfusion and normal FDG uptake; hibernating myocardium exhibits reduced perfusion and normal/enhanced FDG uptake (perfusion/metabolism mismatch), whereas scar tissue is characterized by reduction in both perfusion and FDG uptake (perfusion/metabolism match).
Review Strategy
The Medical Advisory Secretariat used a search strategy similar to that used in the 2001 ICES review to identify English language reports of health technology assessments and primary studies in selected databases, published from January 1, 2001 to April 20, 2005. Patients of interest were those with CAD and severe ventricular dysfunction being considered for revascularization that had undergone viability assessment using either PET and/or other noninvasive techniques. The outcomes of interest were diagnostic and predictive accuracy with respect to recovery of regional or global LV function, long-term survival and cardiac events, and quality of life. Other outcomes of interest were impact on treatment decision, adverse events, and cost-effectiveness ratios.
Of 456 citations, 8 systematic reviews/meta-analyses and 37 reports on primary studies met the selection criteria. The reports were categorized using the Medical Advisory Secretariat levels of evidence system, and the quality of the reports was assessed using the criteria of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) developed by the Centre for Dissemination of Research (National Health Service, United Kingdom). Analysis of sensitivity, specificity, predictive values and likelihood ratios were conducted for all data as well as stratified by mean left ventricular ejection fraction (LVEF). There were no randomized controlled trials. The included studies compared PET with one or more other noninvasive viability tests on the same group of patients or examined the long-term outcomes of PET viability assessments. The quality assessment showed that about 50% or more of the studies had selection bias, interpreted tests without blinding, excluded uninterpretable segments in the analysis, or did not have clearly stated selection criteria. Data from the above studies were integrated with data from the 2001 ICES review for analysis and interpretation.
Summary of Findings
The evidence was derived from populations with moderate to severe ischemic LV dysfunction with an overall quality that ranges from moderate to low.
PET appears to be a safe technique for assessing myocardial viability.
CAD patients with moderate to severe ischemic LV dysfunction and residual viable myocardium had significantly lower 2-year mortality rate (3.2%) and higher event-free survival rates (92% at 3 years) when treated with revascularization than those who were not revascularized but were treated medically (16% mortality at 2-years and 48% 3-year event-free survival).
A large meta-analysis and moderate quality studies of diagnostic accuracy consistently showed that compared to other noninvasive diagnostic tests such as thallium SPECT and echocardiography, FDG PET has:
Higher sensitivity (median 90%, range 71%–100%) and better negative likelihood ratio (median 0.16, range 0–0.38; ideal <0.1) for predicting regional myocardial function recovery after revascularization.
Specificity (median 73%, range 33%–91%) that is similar to other radionuclide imaging but lower than that of dobutamine echocardiography
Less useful positive likelihood ratio (median 3.1, range 1.4 –9.2; ideal>10) for predicting segmental function recovery.
Taking positive and negative likelihood ratios together suggests that FDG PET and dobutamine echocardiography may produce small but sometimes important changes in the probability of recovering regional wall motion after revascularization.
Given its higher sensitivity, PET is less likely to produce false positive results in myocardial viability. PET, therefore, has the potential to identify some patients who might benefit from revascularization, but who would not have been identified as suitable candidates for revascularization using thallium SPECT or dobutamine echocardiography.
PET appears to be superior to other nuclear imaging techniques including SPECT with 201thallium or technetium labelled tracers, although recent studies suggest that FDG SPECT may have comparable diagnostic accuracy as FDG PET for predicting regional and global LV function recovery.
No firm conclusion can be reached about the incremental value of PET over other noninvasive techniques for predicting global function improvement or long-term outcomes in the most important target population (patients with severe ischemic LV dysfunction) due to lack of direct comparison.
An Ontario-based economic analysis showed that in people with CAD and severe LV dysfunction and who were found to have no viable myocardium or indeterminate results by thallium SPECT, the use of PET as a follow-up assessment would likely result in lower cost and better 5-year survival compared to the use of thallium SPECT alone. The projected annual budget impact of adding PET under the above scenario was estimated to range from $1.5 million to $2.3 million.
Conclusion
In patients with severe LV dysfunction, that are deemed to have no viable myocardium or indeterminate results in assessments using other noninvasive tests, PET may have a role in further identifying patients who may benefit from revascularization. No firm conclusion can be drawn on the impact of PET viability assessment on long-term clinical outcomes in the most important target population (i.e. patients with severe LV dysfunction).
PMCID: PMC3385418  PMID: 23074467
6.  Impact of combined 18F-FDG PET/CT in head and neck tumours 
British Journal of Cancer  2005;92(6):1046-1050.
To compare the interobserver agreement and degree of confidence in anatomical localisation of lesions using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18F-FDG PET alone in patients with head and neck tumours. A prospective study of 24 patients (16 male, eight female, median age 59 years) with head and neck tumours was undertaken. 18F-FDG PET/CT was performed for staging purposes. 2D images were acquired over the head and neck area using a GE Discovery LS™ PET/CT scanner. 18F-FDG PET images were interpreted by three independent observers. The observers were asked to localise abnormal 18F-FDG activity to an anatomical territory and score the degree of confidence in localisation on a scale from 1 to 3 (1=exact region unknown; 2=probable; 3=definite). For all 18F-FDG-avid lesions, standardised uptake values (SUVs) were also calculated. After 3 weeks, the same exercise was carried out using 18F-FDG PET/CT images, where CT and fused volume data were made available to observers. The degree of interobserver agreement was measured in both instances. A total of six primary lesions with abnormal 18F-FDG uptake (SUV range 7.2–22) were identified on 18F-FDG PET alone and on 18F-FDG PET/CT. In all, 15 nonprimary tumour sites were identified with 18F-FDG PET only (SUV range 4.5–11.7), while 17 were identified on 18F-FDG PET/CT. Using 18F-FDG PET only, correct localisation was documented in three of six primary lesions, while 18F-FDG PET/CT correctly identified all primary sites. In nonprimary tumour sites, 18F-FDG PET/CT improved the degree of confidence in anatomical localisation by 51%. Interobserver agreement in assigning primary and nonprimary lesions to anatomical territories was moderate using 18F-FDG PET alone (kappa coefficients of 0.45 and 0.54, respectively), but almost perfect with 18F-FDG PET/CT (kappa coefficients of 0.90 and 0.93, respectively). We conclude that 18F-FDG PET/CT significantly increases interobserver agreement and confidence in disease localisation of 18F-FDG-avid lesions in patients with head and neck cancers.
doi:10.1038/sj.bjc.6602464
PMCID: PMC2361926  PMID: 15770212
18F-FDG PET/CT; imaging; head and neck cancers; squamous cell carcinoma
7.  FDG-PET/CT imaging for tumor staging and definition of tumor volumes in radiation treatment planning in non-small cell lung cancer 
Oncology Letters  2014;7(4):1015-1020.
18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) has the potential to improve the staging and radiation treatment (RT) planning of various tumor sites. However, from a clinical standpoint, questions remain with regard to what extent PET/CT changes the target volume and whether PET/CT reduces interobserver variability in target volume delineation. The present study analyzed the use of FDG-PET/CT images for staging and evaluated the impact of FDG-PET/CT on the radiotherapy volume delineation compared with CT in patients with non-small cell lung cancer (NSCLC) who were candidates for radiotherapy. Intraobserver variation in delineating tumor volumes was also observed. In total, 23 patients with stage I-III NSCLC were enrolled and treated with fractionated RT-based therapy with or without chemotherapy. FDG-PET/CT scans were acquired within two weeks prior to RT. PET and CT data sets were sent to the treatment planning system, Pinnacle, through compact discs. The CT and PET images were subsequently fused by means of a dedicated RT planning system. Gross tumor volume (GTV) was contoured by four radiation oncologists on CT (GTV-CT) and PET/CT images (GTV-PET/CT). The resulting volumes were analyzed and compared. For the first phase, two radiation oncologists outlined the contours together, achieving a final consensus. Based on PET/CT, changes in tumor-node-metastasis categories occurred in 8/23 cases (35%). Radiation targeting with fused FDG-PET and CT images resulted in alterations in radiation therapy planning in 12/20 patients (60%) in comparison with CT targeting. The most prominent changes in GTV were observed in cases with atelectasis. For the second phase, the variation in delineating tumor volumes was assessed by four observers. The mean ratio of largest to smallest CT-based GTV was 2.31 (range, 1.01–5.96). The addition of the PET results reduced the mean ratio to 1.46 (range, 1.02–2.27). PET/CT fusion images may have a potential impact on tumor staging and treatment planning. Implementing matched PET/CT results reduced observer variation in delineating tumor volumes significantly with respect to CT only.
doi:10.3892/ol.2014.1874
PMCID: PMC3961455  PMID: 24944661
positron emission tomography/computed tomography; non-small cell lung cancer; radiotherapy; tumor volume
8.  Diagnostic accuracy of integrated 18F-FDG PET/CT for restaging patients with malignant germ cell tumours 
The British Journal of Radiology  2014;87(1040):20140263.
Objective:
Evaluation of utility of fluorine-18 fludeoxyglucose (18F-FDG) positron emission tomography/CT (PET/CT) for restaging patients with primary malignant germ cell tumours (GCTs).
Methods:
Data of 92 patients (age, 31.94 ± 10.1 years; male/female, 86/6) with histopathologically confirmed malignant GCTs (gonadal, 88; mediastinal, 4; seminomatous, 47 and non-seminomatous, 45) who underwent 18F-FDG PET/CT for restaging (suspected recurrence/post-therapy evaluation) were retrospectively analysed. Two experienced nuclear medicine physicians reviewed the PET/CT images in consensus, qualitatively and semi-quantitatively [maximum standardized uptake value (SUVmax)]. Histopathology (if available) and clinical/imaging/biochemical follow-up (minimum of 6 months) were employed as the reference standard.
Results:
18F-FDG PET/CT was interpreted as positive in 59 and negative in 33 patients. Local disease was seen in 5, nodal disease in 50 and distant metastasis in 22 patients. PET/CT was true positive in 49, false positive in 10, true negative in 30 and false negative in 3 patients. 18F-FDG PET/CT showed sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 94.2%, 75.0%, 83.0%, 90.9% and 85.8% overall; 90.0%, 74.0%, 72.0%, 90.9% and 80.8% in seminomatous GCT; and 96.8%, 76.9%, 91.1%, 90.9% and 91.1% in non-seminomatous GCT, respectively. Difference in PET/CT accuracy for seminomatous and non-seminomatous GCTs was not significant (p = 0.263). PET/CT demonstrated disease in 13 patients with negative/equivocal conventional imaging findings and in 9 patients with normal tumour markers. No site- or histology-based difference was seen in SUVmax.
Conclusion:
18F-FDG PET/CT demonstrates high diagnostic accuracy for restaging patients with malignant GCTs. It has comparable diagnostic performance in both seminomatous and non-seminomatous malignant GCTs.
Advances in knowledge:
The present article demonstrates high diagnostic accuracy of 18F-FDG PET/CT for restaging both seminomatous and non-seminomatous malignant GCTs in a large patient population.
doi:10.1259/bjr.20140263
PMCID: PMC4112389  PMID: 24896199
9.  Interobserver Variability in Chest CT and Whole Body FDG-PET Screening for Distant Metastases in Head and Neck Cancer Patients 
Molecular Imaging and Biology  2010;13(2):385-390.
Purpose
The aim of the study was to assess the interobserver variability in chest computed tomography (CT) and whole body 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) screening for distant metastases in head and neck squamous cell carcinoma (HNSCC) patients.
Procedure
Chest CT and whole body FDG-PET of 69 HNSCC patients with high-risk factors who underwent screening for distant metastases were analyzed. All scans were independently read by two experienced radiologists or nuclear physicians who were blinded to the other examinations and follow-up results.
Results
A kappa of 0.516 was found for assessment of size on CT. Kappa values for origin and susceptibility of 0.406 and 0.512 for CT and 0.834 and 0.939 for PET were found, respectively. The overall conclusions had a kappa of 0.517–0.634 for CT and 0.820–1.000 for PET.
Conclusions
In screening for distant metastases in HNSCC patients with high-risk factors, chest CT readings had a reasonable to substantial agreement, while PET readings showed an almost perfect agreement. These findings suggest that for optimal assessment in clinical practice, PET most often can be scored by one observer, but CT should probably more often be scored by different observers in consensus or combined with PET.
doi:10.1007/s11307-010-0354-5
PMCID: PMC3051106  PMID: 20533092
CT; FDG-PET; Interobserver agreement; Distant metastases; Head and neck cancer
10.  Combined use of preoperative 18F FDG-PET imaging and intraoperative gamma probe detection for accurate assessment of tumor recurrence in patients with colorectal cancer 
Background
The purpose of this study was to combine intraoperative gamma probe (GP) detection with preoperative fluorine 18-fluoro-2-deoxy-glucose positron emission tomography (18F FDG-PET) imaging in order to improve detection of tumor recurrence in colorectal cancer (CRC) patients.
Methods
Twenty-one patients (12 females, 9 males) with a mean age of 54 years (range 31–78) were enrolled. Patients were suspected to have recurrent CRC by elevated CEA (n = 11), suspicious CT findings (n = 1), and clinically suspicious findings (n = 9). Preoperative FDG-PET scan and intraoperative GP study were performed in all patients. Mean time interval between preoperative FDG-PET scan and surgery was 16 days (range 1–41 days) in 19 patients. For intraoperative GP studies, 19 patients were injected with a dose of 10–15 mCi 18F FDG at approximately 30 minutes before the planned surgery time. In two patients, the intraoperative GP study was performed immediately after preoperative FDG-PET scan.
Results
Preoperative FDG-PET and intraoperative GP detected 48 and 45 lesions, respectively. A total of 50 presumed site of recurrent disease from 20 patients were resected. Thirty-seven of 50 presumed sites of recurrent disease were histological-proven tumor positive and 13 of 50 presumed sites of recurrent disease were histological-proven tumor negative. When correlated with final histopathology, the number of true positive lesions and false positive lesions by preoperative FDG-PET and intraoperative GP were 31/9 and 35/8, respectively. Both preoperative FDG-PET and intraoperative GP were true positive in 29 lesions. Intraoperative GP detected additional small lesions in the omentum and pelvis which were not seen on preoperative FDG-PET scan. FDG-PET scan demonstrated additional liver metastases which were not detected by intraoperative GP. Preoperative FDG-PET detected distant metastasis in the lung in one patient. The estimated radiation dose received by a surgeon during a single 18F FDG GP surgery was below the occupational limit.
Conclusion
The combined use of preoperative FDG-PET and intraoperative GP is potentially helpful to the surgeon as a roadmap for accurately locating and determining the extent of tumor recurrence in patients with CRC. While intraoperative GP appears to be more sensitive in detecting the extent of abdominal and pelvic recurrence, preoperative FDG-PET appears to be more sensitive in detecting liver metastases. FDG-PET is also a valuable method in detecting distant metastases.
doi:10.1186/1477-7819-5-80
PMCID: PMC1941735  PMID: 17634125
11.  A pilot study of 4′-[methyl-11C]-thiothymidine PET/CT for detection of regional lymph node metastasis in non-small cell lung cancer 
EJNMMI Research  2014;4:10.
Background
4′-[methyl-11C]-thiothymidine (4DST) is a novel positron emission tomography (PET) tracer to assess proliferation of malignancy. The diagnostic abilities of 4DST and 2-deoxy-2-18 F-fluoro-d-glucose (FDG) for detecting regional lymph node (LN) metastases of non-small cell lung cancer (NSCLC) were prospectively compared. In addition, the relationship between the PET result and the patient's prognosis was evaluated.
Methods
A total of 31 patients with NSCLC underwent 4DST PET/computed tomography (CT) and FDG PET/CT. The PET/CT images were evaluated qualitatively and quantitatively for focal uptake of each PET tracer, according to the staging system of the American Joint Committee on Cancer. Surgical and histological results provided the reference standards. Patients were followed for up to two years to assess disease-free survival.
Results
On a per-lesion basis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for LN staging were 82%, 72%, 32%, 96%, and 73%, respectively, for 4DST, and 29%, 86%, 25%, 88%, and 78%, respectively, for FDG. The sensitivity of 4DST was significantly higher than that of FDG (P < 0.001). The disease-free survival rate with positive 4DST uptake in nodal lesions was 0.35, which was considerably lower than the rate of 0.83 with negative findings (P = 0.04). Among the factors tested, nodal staging by 4DST was the most influential prognostic factor (P = 0.05) in predicting the presence of a previously existing spread lesion or of a recurrence over the course of 2 years.
Conclusion
4DST PET/CT is sensitive for detecting mediastinal lymph node metastasis in NSCLC, but its low specificity is a limitation. However, it may be helpful in predicting the prognosis of NSCLC.
doi:10.1186/2191-219X-4-10
PMCID: PMC3976537  PMID: 24593883
4DST; FDG-PET/CT; Lymph node metastasis; Non-small cell lung cancer (NSCLC); Cell proliferation
12.  Prospective use of serial questionnaires to evaluate the therapeutic efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in suspected lung cancer 
Thorax  2003;58(1):47-51.
Background: A study was undertaken to study the effect of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the diagnosis and management of clinically problematic patients with suspected non-small cell lung cancer (NSCLC).
Methods: A prospective before-after study was performed in a cohort of all 164 patients (university/community settings) referred for PET between August 1997 and July 1999. PET was restricted to cases where non-invasive tests had failed to solve clinical problems. The impact on diagnostic understanding and management was assessed using questionnaires (intended treatment without PET, actual treatment choice after PET, post hoc clinical assessment).
Results: Diagnostic problems especially pertained to unclear radiological findings (n=112; 63%), mediastinal staging (n=36; 20%), and distant staging issues (n=16; 9%). PET findings were validated by reviewing medical records. PET had a positive influence on diagnostic understanding in 84%. Improved diagnostic understanding solely based on PET was reported in 26%. According to referring physicians, PET resulted in beneficial change of treatment in 50%. Cancelled surgery was the most frequent change in treatment after PET (35%).
Conclusion: FDG PET applied as "add on" technology in patients with these clinical problems appears to be a clinically useful tool, directly improving treatment choice in 25% of patients. The value of increased confidence induced by PET scanning requires further evaluation.
doi:10.1136/thorax.58.1.47
PMCID: PMC1746467  PMID: 12511720
13.  A case of primary lung cancer lesion demonstrated by F-18 FDG positron emission tomography/computed tomography (PET/CT) one year after the detection of metastatic brain tumor 
Oncology Letters  2011;2(4):621-623.
Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis. Metastatic brain tumors occur in approximately 15% of all cancer patients. F-18 2′-deoxy-2fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) contributes to the evaluation of cancer staging, although the benefits of PET/CT for detection of CUP origins has yet to be determined. In this study, we present a 37-year-old man with a brain tumor detected by magnetic resonance imaging. Surgical biopsy indicated a metastatic undifferentiated carcinoma, while clinical examination and a CT scan did not detect any abnormalities, with the exception of brain metastases. PET/CT did not reveal abnormal FDG uptake. PET/CT revealed abnormal intense FDG uptake in a small nodular lesion in the right lung 1 year following the detection of brain metastasis, and no other abnormal FDG uptake was observed elsewhere in the body. Right upper lobectomy and dissection of mediastinal lymph nodes were performed. The pathological diagnosis was poorly differentiated adenocarcinoma, which was similar to the brain metastatic lesion, and there was no lymph node metastasis. This case revealed an extremely rare lung cancer with primary lesions demonstrated by PET/CT 1 year after the detection of brain metastasis. This case reveals that F-18 FDG PET/CT imaging of CUP origin is capable of positively impacting on the identification of small primary tumor foci.
doi:10.3892/ol.2011.318
PMCID: PMC3406449  PMID: 22848237
PET/CT; metastatic brain tumor; lung cancer; unknown primary origin
14.  Early Detection of Erlotinib Treatment Response in NSCLC by 3′-Deoxy-3′-[18F]-Fluoro-L-Thymidine ([18F]FLT) Positron Emission Tomography (PET) 
PLoS ONE  2008;3(12):e3908.
Background
Inhibition of the epidermal growth factor receptor (EGFR) has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). Somatic mutations of EGFR were found in lung adenocarcinoma that lead to exquisite dependency on EGFR signaling; thus patients with EGFR-mutant tumors are at high chance of response to EGFR inhibitors. However, imaging approaches affording early identification of tumor response in EGFR-dependent carcinomas have so far been lacking.
Methodology/Principal Findings
We performed a systematic comparison of 3′-Deoxy-3′-[18F]-fluoro-L-thymidine ([18F]FLT) and 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) for their potential to identify response to EGFR inhibitors in a model of EGFR-dependent lung cancer early after treatment initiation. While erlotinib-sensitive tumors exhibited a striking and reproducible decrease in [18F]FLT uptake after only two days of treatment, [18F]FDG PET based imaging revealed no consistent reduction in tumor glucose uptake. In sensitive tumors, a decrease in [18F]FLT PET but not [18F]FDG PET uptake correlated with cell cycle arrest and induction of apoptosis. The reduction in [18F]FLT PET signal at day 2 translated into dramatic tumor shrinkage four days later. Furthermore, the specificity of our results is confirmed by the complete lack of [18F]FLT PET response of tumors expressing the T790M erlotinib resistance mutation of EGFR.
Conclusions
[18F]FLT PET enables robust identification of erlotinib response in EGFR-dependent tumors at a very early stage. [18F]FLT PET imaging may represent an appropriate method for early prediction of response to EGFR TKI treatment in patients with NSCLC.
doi:10.1371/journal.pone.0003908
PMCID: PMC2592703  PMID: 19079597
15.  A Prospective Analysis of Positron Emission Tomography and Conventional Imaging for Detection of Stage IV Metastatic Melanoma in Patients Undergoing Metastasectomy 
Annals of surgical oncology  2004;11(8):731-738.
Background
Positron emission tomography with 2-deoxy-2-[18F]fluoro-d-glucose (FDG-PET) is available for evaluation of patients with melanoma. This study evaluates the potential of FDG-PET to improve on conventional imaging (CI) in patients with stage IV melanoma undergoing metastasectomy.
Methods
This was a prospective study comparing radiological evaluation of patients who underwent metastasectomy for palliation or cure. Patients underwent preoperative evaluation by physical examination, CI by computed tomography and/or magnetic resonance imaging, and FDG-PET. Independent observers performed three separate analyses of CI alone, FDG-PET alone, or FDG-PET read with knowledge of CI (FDG-PET + CI). Abnormalities were reported as benign or malignant and assessed by pathologic analysis or by clinical outcome determined by disease progression detected on serial evaluations.
Results
Ninety-four lesions were noted in 18 patients who underwent preoperative assessment, metastasectomy, and long-term follow up (median, 24 months). Lesion-by-lesion analysis for CI demonstrated a sensitivity of 76%, a specificity of 87%, a positive predictive value (PPV) of 86%, and a negative predictive value (NPV) of 76%. FDG-PET demonstrated a sensitivity of 79%, a specificity of 87%, a PPV of 86%, and an NPV of 80%. For FDG-PET + CI, the sensitivity was 88%, specificity was 91%, and PPV and NPV were 91% and 88%, respectively.
Conclusions
Combined use of FDG-PET and CI may be an accurate strategy to identify sites of disease in patients with stage IV melanoma being considered for metastasectomy. Interpreted independently, FDG-PET and CI seemed to be equivalent modalities. FDG-PET + CI had both the highest sensitivity on lesion-by-lesion analysis and the best accuracy on patient-by-patient analysis.
doi:10.1245/ASO.2004.01.023
PMCID: PMC2227906  PMID: 15249335
Melanoma; Cancer; FDG-PET; Imaging; Metastasectomy; Surgery
16.  P46. Use of 18-FDG PET/CT in the radiotherapy planning of lung cancer—our updated experiences 
Purpose
To compare the definition of gross tumor volume using computed tomography (CT) alone versus 18-FDG positron emission tomography/computed tomography (PET/CT), show the role of integration of PET in radiotherapy planning and its impact on definition of the planning target volume, for its coverage by prescribed dose and the dose to the lung in patients with non-small lung cancer (NSCLC).
Material and methods
Total of 40 patients with non-small cell lung cancer underwent three-dimensional conformal radiotherapy (3D CRT). Before radiotherapy planning, there were performed 18-FDG PET/CT or CT alone in all of patients. Three groups of gross tumor volumes were defined: Group 1: CT volumes alone (CT-tumor and CT-lymph nodes); Group 2: PET volumes alone (PET-tumor and PET-lymph nodes); Group 3: fused PET with CT volumes (fused PET/CT-tumor and fused PET/CT-lymph nodes). The median total dose was 66 Gy, 1.8-2 Gy per day, 5 times a week (min =30 Gy, max=70 Gy). There were compared two 3D-CRT plans (AP-PA or oblique fields, three fields or four fields) with respect to the gross tumor volume (GTV), planning target volume (PTV), the mean lung dose (MLD) and lung volume which received ≥20 Gy (V20).
Results
Several studies have addressed with possibility of using 18-FDG PET in radiotherapy contouring of individual volumes to improve the overall accuracy and reduce interobserver variability. The biggest changes in the definition of gross tumor volume were recorded in cases of atelectasis and in the definition of affected mediastinal lymph nodes which were not clearly differentiable by CT alone. Improvement of the target volume coverage and reduction of the target volume using 18-FDG PET/CT in the planning of radiotherapy leads to the possibility of dose escalation to the tumor and reduction to the surrounding healthy tissues. Information obtained by 18 FDG-PET enabled to significantly reduce the endpoints: GTV at 40%, PTV at 68%, MLD at 64%, and V20 at 68% patients. Use of PET/CT in the radiotherapy planning causes a reduction in dose to lung (median =17 Gy MLD-CT versus MLD-PET/CT =12 Gy; median =29% V20-CT versus V20-PET/CT =21%).
Conclusions
Although the target volumes defined by CT are similar to the target volumes defined by PET, but more often were the cases that the use of CT alone without fusion with PET occurred under-dosage, and not covered the entire target volume. Radiotherapy treatment planning by PET/CT is more accurate in terms of definition of tumor and lymph nodes and more accurate differentiation atelectasis from the tumor than by CT alone.
doi:10.3978/j.issn.2218-6751.2014.AB058
PMCID: PMC4367749
Non-small lung cancer (NSCLC); positron emission tomography/computed tomography (PET-CT); radiotherapy
17.  Lymph node staging in non-small cell lung cancer: evaluation by [18F]FDG positron emission tomography (PET) 
Thorax  1997;52(5):438-441.
BACKGROUND: A study was undertaken to investigate the accuracy of positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D- glucose (FDG) in the thoracic lymph node staging of non-small cell lung cancer (NSCLC). METHODS: Forty six patients with focal pulmonary tumours who underwent preoperative computed tomographic (CT) and FDG- PET scanning were evaluated retrospectively. Thirty two patients had NSCLC and 14 patients had a benign process. The final diagnosis was established by means of histopathological examination at thoracotomy, and the nodal classification in patients with lung cancer was performed by thorough dissection of the mediastinal nodes at surgery. RESULTS: FDG-PET was 80% sensitive, 100% specific, and 87.5% accurate in staging thoracic lymph nodes in patients with NSCLC, whereas CT scanning was 50% sensitive, 75% specific, and 59.4% accurate. The absence of lymph node tumour involvement was identified by FDG-PET in all 12 patients with NO disease compared with nine by CT scanning. Lymph node metastases were correctly detected by FDG-PET in three of five patients with N1 disease compared with two by CT scanning, in nine of 11 with N2 disease compared with six by CT scanning, an in all four with N3 nodes compared with two by CT scanning. CONCLUSIONS: FDG-PET provides a new and effective method for staging thoracic lymph nodes in patients with lung cancer and is superior to CT scanning in the assessment of hilar and mediastinal nodal metastases. With regard to resectability, FDG-PET could differentiate reliably between patients with N1/N2 disease and those with unresectable N3 disease. 



PMCID: PMC1758560  PMID: 9176535
18.  Roles of computed tomography and [18F]fluorodeoxyglucose-positron emission tomography/computed tomography in the characterization of multiple solitary solid lung nodules 
ecancermedicalscience  2012;6:266.
The purpose of this study is to compare the performance of multidetector computed tomography (CT) and positron emission tomography/CT (PET/CT) with [18F]fluorodeoxyglucose in the diagnosis of multiple solitary lung nodules in 14 consecutive patients with suspicious lung cancer. CT and PET/CT findings were reviewed by a radiologist and nuclear medicine physician, respectively, blinded to the pathological diagnoses of lung cancer, considering nodule size, shape, and location (CT) and maximum standardized uptake value normalized to body weight (SUVbw max). Nodules were judged malignant or benign. The sensitivity, specificity, and accuracy of the two techniques were compared. CT had a sensitivity, specificity, and accuracy of 93.7, 86.7, and 90.3%, respectively, whereas PET/CT had a sensitivity, specificity, and accuracy of 75, 100, and 87.1%, respectively. Clinical management would have been erroneous in two patients by CT alone and in four patients by PET/CT alone. In one patient, the two techniques misdiagnosed the nodules (2 CT and 1 PET/CT). CT and PET/CT have complimentary roles in characterization of multiple solitary pulmonary nodules. Small nodules are poorly characterized by CT, and small-sized low-SUV malignant nodules are difficult to detect with PET/CT.
doi:10.3332/ecancer.2012.266
PMCID: PMC3430489  PMID: 22949928
19.  FDG-PET scan in patients with clinically and/or radiologically suspicious colorectal cancer recurrence but normal CEA 
Background
Although frequently used for tumor surveillance, the sensitivity of carcinoembryonic antigen (CEA) to detect recurrent colorectal cancer (CRC) is not optimal. Fluorine 18-fluoro-2-deoxy-glucose-positron emission tomography (18F FDG-PET) scans promise to improve recurrent CRC detection. We aimed to review PET scans of patients with clinically and/or radiologically suspicious tumor recurrence but normal CEA.
Methods
A retrospective review of an electronic database of 308 patients with CRC who had PET scans was performed. Only PET studies of patients with normal CEAs and suspected tumor recurrence who had pathological verification were selected for further analysis. Thirty-nine patients met the inclusion criteria.
Results
PET was positive in 26 patients (67%) and normal in 13 (33%). Histopathologic evidence of tumor recurrence was seen in 27 of the 39 patients (69%). When correlated with histopathology, PET was true positive in 22 patients, false positive in 4, true negative in 8 and false negative in 5. Overall, the accuracy of PET was 76.9%, negative predictive value (NPV) was 61.5%, and positive predictive value (PPV) was 84.6%. PPV value of PET for liver metastases was 88.8% compared to 73.3% for local recurrence. In two patients with confirmed recurrence, CEA became positive 2 months after PET scan indicating earlier detection of disease with PET. The false positive PET findings were mainly in the bowel and were secondary to acute/chronic inflammation and granulation tissue. In 3 patients with false negative PET, histopathology was consistent with mucinous adenocarcinoma.
Conclusion
PET yields high PPV for recurrent CRC, particularly for liver metastases, in spite of normal CEA levels and should be considered early in the evaluation of patients with suspected tumor recurrence.
doi:10.1186/1477-7819-5-64
PMCID: PMC1896164  PMID: 17555577
20.  A computational pipeline for quantification of pulmonary infections in small animal models using serial PET-CT imaging 
EJNMMI Research  2013;3:55.
Background
Infectious diseases are the second leading cause of death worldwide. In order to better understand and treat them, an accurate evaluation using multi-modal imaging techniques for anatomical and functional characterizations is needed. For non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), there have been many engineering improvements that have significantly enhanced the resolution and contrast of the images, but there are still insufficient computational algorithms available for researchers to use when accurately quantifying imaging data from anatomical structures and functional biological processes. Since the development of such tools may potentially translate basic research into the clinic, this study focuses on the development of a quantitative and qualitative image analysis platform that provides a computational radiology perspective for pulmonary infections in small animal models. Specifically, we designed (a) a fast and robust automated and semi-automated image analysis platform and a quantification tool that can facilitate accurate diagnostic measurements of pulmonary lesions as well as volumetric measurements of anatomical structures, and incorporated (b) an image registration pipeline to our proposed framework for volumetric comparison of serial scans. This is an important investigational tool for small animal infectious disease models that can help advance researchers’ understanding of infectious diseases.
Methods
We tested the utility of our proposed methodology by using sequentially acquired CT and PET images of rabbit, ferret, and mouse models with respiratory infections of Mycobacterium tuberculosis (TB), H1N1 flu virus, and an aerosolized respiratory pathogen (necrotic TB) for a total of 92, 44, and 24 scans for the respective studies with half of the scans from CT and the other half from PET. Institutional Administrative Panel on Laboratory Animal Care approvals were obtained prior to conducting this research. First, the proposed computational framework registered PET and CT images to provide spatial correspondences between images. Second, the lungs from the CT scans were segmented using an interactive region growing (IRG) segmentation algorithm with mathematical morphology operations to avoid false positive (FP) uptake in PET images. Finally, we segmented significant radiotracer uptake from the PET images in lung regions determined from CT and computed metabolic volumes of the significant uptake. All segmentation processes were compared with expert radiologists’ delineations (ground truths). Metabolic and gross volume of lesions were automatically computed with the segmentation processes using PET and CT images, and percentage changes in those volumes over time were calculated. (Continued on next page)(Continued from previous page) Standardized uptake value (SUV) analysis from PET images was conducted as a complementary quantitative metric for disease severity assessment. Thus, severity and extent of pulmonary lesions were examined through both PET and CT images using the aforementioned quantification metrics outputted from the proposed framework.
Results
Each animal study was evaluated within the same subject class, and all steps of the proposed methodology were evaluated separately. We quantified the accuracy of the proposed algorithm with respect to the state-of-the-art segmentation algorithms. For evaluation of the segmentation results, dice similarity coefficient (DSC) as an overlap measure and Haussdorf distance as a shape dissimilarity measure were used. Significant correlations regarding the estimated lesion volumes were obtained both in CT and PET images with respect to the ground truths (R2=0.8922,p<0.01 and R2=0.8664,p<0.01, respectively). The segmentation accuracy (DSC (%)) was 93.4±4.5% for normal lung CT scans and 86.0±7.1% for pathological lung CT scans. Experiments showed excellent agreements (all above 85%) with expert evaluations for both structural and functional imaging modalities. Apart from quantitative analysis of each animal, we also qualitatively showed how metabolic volumes were changing over time by examining serial PET/CT scans. Evaluation of the registration processes was based on precisely defined anatomical landmark points by expert clinicians. An average of 2.66, 3.93, and 2.52 mm errors was found in rabbit, ferret, and mouse data (all within the resolution limits), respectively. Quantitative results obtained from the proposed methodology were visually related to the progress and severity of the pulmonary infections as verified by the participating radiologists. Moreover, we demonstrated that lesions due to the infections were metabolically active and appeared multi-focal in nature, and we observed similar patterns in the CT images as well. Consolidation and ground glass opacity were the main abnormal imaging patterns and consistently appeared in all CT images. We also found that the gross and metabolic lesion volume percentage follow the same trend as the SUV-based evaluation in the longitudinal analysis.
Conclusions
We explored the feasibility of using PET and CT imaging modalities in three distinct small animal models for two diverse pulmonary infections. We concluded from the clinical findings, derived from the proposed computational pipeline, that PET-CT imaging is an invaluable hybrid modality for tracking pulmonary infections longitudinally in small animals and has great potential to become routinely used in clinics. Our proposed methodology showed that automated computed-aided lesion detection and quantification of pulmonary infections in small animal models are efficient and accurate as compared to the clinical standard of manual and semi-automated approaches. Automated analysis of images in pre-clinical applications can increase the efficiency and quality of pre-clinical findings that ultimately inform downstream experimental design in human clinical studies; this innovation will allow researchers and clinicians to more effectively allocate study resources with respect to research demands without compromising accuracy.
doi:10.1186/2191-219X-3-55
PMCID: PMC3734217  PMID: 23879987
Quantitative analysis; Pulmonary infections; Small animal models; PET-CT; Image segmentation; H1N1; Tuberculosis
21.  Influence of Introduction of Positron Emission Tomography on Adherence to Mediastinal Staging Protocols and Performance of Mediastinoscopy 
Journal of Oncology Practice  2007;3(5):242-247.
Purpose
In this study, we investigated the impact of implementation of [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) in daily practice on adherence to mediastinal staging protocols and performance of mediastinoscopy in non–small-cell lung cancer (NSCLC) patients who are possible candidates for surgical resection. Institutional review board approval was obtained.
Patients and Methods
From a nonuniversity teaching hospital and three surrounding community hospitals in Eindhoven, the Netherlands, we studied data from 143 patients with NSCLC who underwent mediastinoscopy and/or thoracotomy in three consecutive periods (1, 0 to 9 months; 2, 10 to 18 months; and 3, 19 to 31 months) after introduction of PET. Mediastinoscopy was indicated in case of enlarged and/or PET-positive nodes. Adherence to these surgical mediastinal staging guidelines and the performance of PET and mediastinoscopy were investigated and compared between the three periods and with our previous study before introduction of PET.
Results and Conclusion
Guidelines for indicating mediastinoscopy were adequately followed in significantly more instances after introduction of PET (80%), compared with the period before PET (66%). Optimal yield (lymph node stations 4, right and left, and 7) of mediastinoscopy (in 27% of patients) was not significantly different from the period before PET (39% of patients). Compared with the historical data, the percentage of positive mediastinoscopies increased from 15.5 to 17.6 (not significant). We found no significant differences between the three consecutive periods with regard to adequacy of indicating and performance of mediastinoscopy. After introduction of PET, adherence to staging guidelines with respect to mediastinoscopy improved. Although fewer mediastinoscopies had an optimal yield, more proved to be positive for metastases. Nevertheless, when a mediastinoscopy is indicated, surgeons must be encouraged to reach an optimal yield because PET positive nodes might be false negative. This occurred in 5% to 6% of all patients.
doi:10.1200/JOP.0752002
PMCID: PMC2793831  PMID: 20859419
22.  The role of 18F-FDG-PET/CT in the preoperative staging and posttherapy follow up of gastriccancer:Comparison with spiral CT 
Background
The aim of this study was to investigate the role of F-18 fluoro-deoxy-glucose (FDG) positron emission tomography and computed tomography (PET/CT) in the preoperative and posttherapy restaging of gastric cancer and to compare with spiral computerized tomography (CT).
Method
A total of 42 PET/CT scans of 36 gastric cancer patients (28M, 8F; mean age: 56,0 ± 15) were included in the study. A retrospective analysis of the PET/CT results of the patients were compared with concurrent CT results. Confirmation was made by clinical course and serial imaging studies in the follow up. The compatibility ratios were calculated and the accuracy of the PET/CT was assessed. Agreement between PET/CT and concurrent CT was calculated using kappa statistics.
Results
Patients were separated into 3 groups: the patients who were referred to our clinic for preoperative staging (4 patients), for posttherapy evaluation (24 patients) and for the suspicion of local recurrence and/or metastasis exploration after a disease free period (8 patients). Groups 1 and 3 included a small number of patients so they were omitted from the statistical analysis. Focusing on Goup 2, the overall concordance rate was 50% (12 patients). Region based analysis showed the rates of concordance for local recurrence, local lymph node metastasis and distant metastasis were 91% (Kappa: 0.70), 95% (Kappa:0.86) and 50% (Kappa:0.26) respectively. Distant metastases were also investigated in detail and the two techniques showed a concordance of 91% (Kappa: 0.75) for liver, 79%(Kappa:0.31) for distant lymph node, 79% (0.42) for lung, 87%(Kappa:0.33) for bone and 95% for intestinal wall metastasis.
Conclusion
PET/CT is a complementary imaging method which can be successfully used in both preoperative and posttherapy evaluation of gastric cancer.
doi:10.1186/1477-7819-9-75
PMCID: PMC3148984  PMID: 21752303
Gastric cancer; FDG-PET/CT; spiral CT
23.  Diagnostic usefulness of an amino acid tracer, α-[N-methyl-11C]-methylaminoisobutyric acid (11C-MeAIB), in the PET diagnosis of chest malignancies 
Annals of Nuclear Medicine  2013;27(9):808-821.
Objectives
Although positron emission tomography (PET) using [18F]-fluoro-2-deoxy-d-glucose (18F-FDG) is established as one of the first-choice imaging modalities in the diagnosis of chest malignancies, there are several problems to solve in clinical practice, such as false positive uptake in inflammatory diseases. The aim of this study was to evaluate the clinical usefulness of an amino acid tracer, α-[N-methyl-11C]-methylaminoisobutyric acid (11C-MeAIB), in the diagnosis of chest malignancies, in combination with 18F-FDG.
Setting
Fifty-nine cases (57 patients, 66 ± 12 years old) who consulted to our institution for the wish to receive differential diagnosis of chest diseases were included. Purpose of the studies were as follows: differential diagnosis of newly developed lung nodules, n = 22; newly developed mediastinal lesions, n = 20; and both, n = 17 (including lung cancer: n = 19, lymphoma: n = 1, other cancers: n = 2, sarcoidosis: n = 15, non-specific inflammation: n = 18, other inflammatory: n = 4, respectively). Whole-body static PET or PET/CT scan was performed 20 and 50 min after the IV injection of 11C-MeAIB and 18F-FDG, respectively.
Results
11C-MeAIB uptake of malignant and benign lesions was statistically different both in pulmonary nodules (p < 0.005) and in mediastinal lesions (p < 0.0005). In visual differential diagnosis, 11C-MeAIB showed higher results (specificity: 73 %, accuracy: 81 %), compared to those in 18F-FDG (60, 73 %, respectively). In cases of sarcoidosis, 11C-MeAIB showed higher specificity (80 %) with lower uptake (1.8 ± 0.7) in contrast to the lower specificity (60 %) with higher uptake of 18F-FDG (7.3 ± 4.5).
Conclusions
11C-MeAIB PET/CT was useful in the differential diagnosis of pulmonary and mediastinal mass lesions found on CT. 11C-MeAIB PET or PET/CT showed higher specificity than that of 18F-FDG PET/CT in differentiating between benign and malignant disease. Our data suggest that the combination of 18F-FDG and 11C-MeAIB may improve the evaluation of chest lesions, when CT and 18F-FDG PET/CT are equivocal.
doi:10.1007/s12149-013-0750-4
PMCID: PMC3830191  PMID: 23824782
Amino acid tracer; Methylaminoisobutyric acid; Fluorodeoxyglucose; Lung cancer; Lymphadenopathy; Positron emission tomography; Sarcoidosis
24.  Positron emission tomography in ovarian cancer: 18F-deoxy-glucose and 16α-18F-fluoro-17β-estradiol PET 
The most frequently used molecular imaging technique is currently 18F-deoxy-glucose (FDG) positron emission tomography (PET). FDG-PET holds promise in the evaluation of recurrent or residual ovarian cancer when CA125 levels are rising and conventional imaging, such as ultrasound, CT, or MRI, is inconclusive or negative. Recently, integrated PET/CT, in which a full-ring-detector clinical PET scanner and a multidetector helical CT scanner are combined, has enabled the acquisition of both metabolic and anatomic imaging data using one device in a single diagnostic session. This can also provide precise anatomic localization of suspicious areas of increased FDG uptake and rule out false-positive PET findings. FDG-PET/CT is an accurate modality for assessing primary and recurrent ovarian cancer and may affect management. FDG-PET/CT may provide benefits for detection of recurrent of ovarian cancer and improve surgical planning. And FDG-PET has been shown to predict response to neoadjuvant chemotherapy and survival in advanced ovarian cancer. This review focuses on the role of FDG-PET and FDG-PET/CT in the management of patients with ovarian cancer. Recently, we have evaluated 16α-18F-fluoro-17β-estradiol (FES)-PET, which detects estrogen receptors. In a preliminary study we reported that FES-PET provides information useful for assessing ER status in advanced ovarian cancer. This new information may expand treatment choice for such patients.
doi:10.1186/1757-2215-2-7
PMCID: PMC2702339  PMID: 19527525
25.  Using pet-ct to reduce futile thoracotomy rates in non-small-cell lung cancer: a population-based review 
Current Oncology  2014;21(6):e768-e774.
Background
Combined positron-emission tomography and computed tomography (pet-ct) reduces futile thoracotomy (ft) rates in patients with non-small-cell lung cancer (nsclc). We sought to identify preoperative risk factors for ft in patients staged with pet-ct.
Methods
We retrospectively reviewed all patients referred to the BC Cancer Agency during 2009–2010 who underwent pet-ct and thoracotomy for nsclc. Patients with clinical N2 disease were excluded. An ft was defined as any of a benign lesion; an exploratory thoracotomy; pathologic N2 or N3, stage iiib or iv, or inoperable T3 or T4 disease; and recurrence or death within 1 year of surgery.
Results
Of the 108 patients who met the inclusion criteria, ft occurred in 27. The main reason for ft was recurrence within 1 year (14 patients) and pathologic N2 disease (10 patients). On multivariate analysis, an Eastern Cooperative Oncology Group performance status greater than 1, a pet-ct positive N1 status, a primary tumour larger than 3 cm, and a period of more than 16 weeks from pet-ct to surgery were associated with ft. N2 disease that had been negative on pet-ct occurred in 21% of patients with a pet-ct positive N1 status and in 20% of patients with tumours larger than 3 cm and non-biopsy mediastinal staging only. The combination of pet-ct positive N1 status and a primary larger than 3 cm had 85% specificity, and the presence of either risk factor had 100% sensitivity, for ft attributable to N2 disease.
Conclusions
To reduce ft attributable to N2 disease, tissue biopsy for mediastinal staging should be considered for patients with pet-ct positive N1 status and with tumours larger than 3 cm even with a pet-ct negative mediastinum.
doi:10.3747/co.21.2125
PMCID: PMC4257121  PMID: 25489265
Non-small-cell lung cancer; positron-emission tomography–computed tomography; thoracotomy; lymphatic metastasis or pathology; mediastinal staging; endobronchial ultrasonography; mediastinoscopy; endoscopic ultrasonography

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