Reproducibility of [18F]MK-6240 kinetics in brain studies with shortened dynamic PET protocol in healthy/cognitively normal subjects.

BACKGROUND: [18F]MK-6240 is a neurofibrillary tangles PET radiotracer that has been broadly used in aging and Alzheimer's disease (AD) studies. Majority of [18F]MK-6240 PET studies use dynamic acquisitions longer than 60 min to assess the tracer kinetic parameters. As of today, no consensus has been established on the optimum dynamic PET scan time. In this study, we assess the reproducibility of [18F]MK-6240 quantitative metrics using shortest dynamic PET protocols in cognitively normal subjects. PET metrics were measured through two-tissue compartment model (2TCM) and Logan model to estimate VT and DVR, as well as SUVR from 90 to 120 min (SUVR90 - 120 min) post-tracer injection for brain regions. 2TCM was carried out using the 120 min dynamic coffee break dataset (first scan from 0 to 60 min p.i., second scan from 90 to 120 min p.i.) and then repeated after stepwise shortening it by 5 min. The dynamic scan length that reproduced the 120 min dynamic scans-based VT to within 10% error was defined as the shortest acquisition time (SAT). The SAT SUVR90 - 120 min was deduced from the SAT dataset by extrapolation of each image pixel time-activity curve to 120 min. The reproducibility of the 120 min dynamic scans-based VT2TCM, DVR2TCM, DVRLogan, and SUVR using the SAT was assessed using Passing-Bablock analysis. The limits of reproducibility of each PET metrics were determined using Bland-Altman analysis. RESULTS: A dynamic SAT of 40 min yielded < 10% error in [18F]MK-6240 VT2TCM's for all brain regions, compared to those measured using the 120 min datasets. SAT-based analysis did not show statistically significant systemic or proportional biases in VT2TCM, DVR2TCM, DVRLogan, or SUVR compared to those deduced from the full dynamic dataset of 120 min. A mean difference between the 120 min- and SAT-based analysis of less than 4%, 10%, 15%, and 20% existed in the VT2TCM, DVR2TCM, DVRLogan, and SUVR respectively. CONCLUSION: Kinetic modeling of [18F]MK-6240 PET can be accurately performed using dynamic scan times as short as 40 min. This can facilitate studies with [18F]MK-6240 PET and improve patients accrual. Further work would be necessary to confirm the reproducibility of these results for patients in dementia spectra.

The potential of a medium-cost long axial FOV PET system for nuclear medicine departments.

PURPOSE: Total body positron emission tomography (TB-PET) has recently been introduced in nuclear medicine departments. There is a large interest in these systems, but for many centers, the high acquisition cost makes it very difficult to justify their current operational budget. Here, we propose medium-cost long axial FOV scanners as an alternative. METHODS: Several medium-cost long axial FOV designs are described with their advantages and drawbacks. We describe their potential for higher throughput, more cost-effective scanning, a larger group of indications, and novel research opportunities. The wider spread of TB-PET can also lead to the fast introduction of new tracers (at a low dose), new methodologies, and optimized workflows. CONCLUSIONS: A medium-cost TB-PET would be positioned between the current standard PET-CT and the full TB-PET systems in investment but recapitulate most advantages of full TB-PET. These systems could be more easily justified financially in a standard academic or large private nuclear medicine department and still have ample research options.

Physical performance of adaptive axial FOV PET scanners with a sparse detector block rings or a checkerboard configuration.

Objective.Using Monte-Carlo simulations, we evaluated the physical performance of a hypothetical state-of-the-art clinical PET scanner with adaptive axial field-of-view (AFOV) based on the validated GATE model of the Siemens Biograph VisionTMPET/CT scanner.Approach.Vision consists of 16 compact PET rings, each consisting of 152 mini-blocks of 5 × 5 Lutetium Oxyorthosilicate crystals (3.2 × 3.2 × 20 mm3). The Vision 25.6 cm AFOV was extended by adopting (i) a sparse mini-block ring (SBR) configuration of 49.6 cm AFOV, with all mini-block rings interleaved with 16 mm axial gaps, or (ii) a sparse mini-block checkerboard (SCB) configuration of 51.2 cm AFOV, with all mini-blocks interleaved with gaps of 16 mm (transaxial) × 16 mm (axial) width in checkerboard pattern. For sparse configurations, a 'limited' continuous bed motion (limited-CBM) acquisition was employed to extend AFOVs by 2.9 cm. Spatial resolution, sensitivity, image quality (IQ), NECR and scatter fraction were assessed per NEMA NU2-2012.Main Results.All IQ phantom spheres were distinguishable with all configurations. SBR and SCB percent contrast recovery (% CR) and background variability (% BV) were similar (p-value > 0.05). Compared to Vision, SBR and SCB %CRs were similar (p-values > 0.05). However, SBR and SCB %BVs were deteriorated by 30% and 26% respectively (p-values < 0.05). SBR, SCB and Vision exhibited system sensitivities of 16.6, 16.8, and 15.8 kcps MBq-1, NECRs of 311 kcps @35 kBq cc-1, 266 kcps @25.8 kBq cc-1, and 260 kcps @27.8 kBq cc-1, and scatter fractions of 31.2%, 32.4%, and 32.6%, respectively. SBR and SCB exhibited a smoother sensitivity reduction and noise enhancement rate from AFOV center to its edges. SBR and SCB attained comparable spatial resolution in all directions (p-value > 0.05), yet, up to 1.5 mm worse than Vision (p-values < 0.05).Significance.The proposed sparse configurations may offer a clinically adoptable solution for cost-effective adaptive AFOV PET with either highly-sensitive or long-AFOV acquisitions.

Assessing Bone Marrow Activity with [18F]FLT PET in Patients with Essential Thrombocythemia and Prefibrotic Myelofibrosis: A Proof of Concept.

Objectives: This study aims to assess the value of FLT-PET as a non-invasive tool to differentiate between patients with ET and Pre-PMF. This study is a pilot study to have a proof of concept only. Methods: This is a prospective, interventional study where a total of 12 patients were included. Each patient underwent FLT PET imaging as well as bone marrow examination (gold standard). In addition, semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen, and Lspine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of <.05 is considered to be statistically significant. Results: The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P > .05). In contrast, TLG measurements in the LSpine were statistically different (P = .013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion: This study is a proof of concept about the potential to discriminate between ET and pre-PMF patients in a non-invasive way. TLG of the LSpine in FLT PET images is a potential quantitative parameter to distinguish between ET and pre-PMF patients.

Population-based input function for TSPO quantification and kinetic modeling with [11C]-DPA-713.

INTRODUCTION: Quantitative positron emission tomography (PET) studies of neurodegenerative diseases typically require the measurement of arterial input functions (AIF), an invasive and risky procedure. This study aims to assess the reproducibility of [11C]DPA-713 PET kinetic analysis using population-based input function (PBIF). The final goal is to possibly eliminate the need for AIF. MATERIALS AND METHODS: Eighteen subjects including six healthy volunteers (HV) and twelve Parkinson disease (PD) subjects from two [11C]-DPA-713 PET studies were included. Each subject underwent 90 min of dynamic PET imaging. Five healthy volunteers underwent a test-retest scan within the same day to assess the repeatability of the kinetic parameters. Kinetic modeling was carried out using the Logan total volume of distribution (VT) model. For each data set, kinetic analysis was performed using a patient-specific AIF (PSAIF, ground-truth standard) and then repeated using the PBIF. PBIF was generated using the leave-one-out method for each subject from the remaining 17 subjects and after normalizing the PSAIFs by 3 techniques: (a) Weightsubject×DoseInjected, (b) area under AIF curve (AUC), and (c) Weightsubject×AUC. The variability in the VT measured with PSAIF, in the test-retest study, was determined for selected brain regions (white matter, cerebellum, thalamus, caudate, putamen, pallidum, brainstem, hippocampus, and amygdala) using the Bland-Altman analysis and for each of the 3 normalization techniques. Similarly, for all subjects, the variabilities due to the use of PBIF were assessed. RESULTS: Bland-Altman analysis showed systematic bias between test and retest studies. The corresponding mean bias and 95% limits of agreement (LOA) for the studied brain regions were 30% and ± 70%. Comparing PBIF- and PSAIF-based VT estimate for all subjects and all brain regions, a significant difference between the results generated by the three normalization techniques existed for all brain structures except for the brainstem (P-value = 0.095). The mean % difference and 95% LOA is -10% and ±45% for Weightsubject×DoseInjected; +8% and ±50% for AUC; and +2% and ± 38% for Weightsubject×AUC. In all cases, normalizing by Weightsubject×AUC yielded the smallest % bias and variability (% bias = ±2%; LOA = ±38% for all brain regions). Estimating the reproducibility of PBIF-kinetics to PSAIF based on disease groups (HV/PD) and genotype (MAB/HAB), the average VT values for all regions obtained from PBIF is insignificantly higher than PSAIF (%difference = 4.53%, P-value = 0.73 for HAB; and %difference = 0.73%, P-value = 0.96 for MAB). PBIF also tends to overestimate the difference between PD and HV for HAB (% difference = 32.33% versus 13.28%) and underestimate it in MAB (%difference = 6.84% versus 20.92%). CONCLUSIONS: PSAIF kinetic results are reproducible with PBIF, with variability in VT within that obtained for the test-retest studies. Therefore, VT assessed using PBIF-based kinetic modeling is clinically feasible and can be an alternative to PSAIF.

Comparison of FDG and FMISO uptakes and distributions in head and neck squamous cell cancer tumors.

PURPOSE: Glycolysis is increased by hypoxia, suggesting a possible correlation between the accumulation of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in malignant tumors and regional hypoxia defined by 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole (FMISO) PET. The aim of this study is to investigate the intra-tumoral spatial distribution and quantitative relationship between FDG and FMISO in a cohort of head and neck squamous cell cancer (HNSCC) patients. METHODS: Twenty HNSCC patients with 20 primary tumors and 19 metastatic lymph nodes (LNs) underwent FDG and FMISO PET within 1 week. The metabolic target volume (MTV) was defined on the FDG PET images using a region growing algorithm. The hypoxic volume (HV) was defined by the volume of voxels in an FMISO image within the MTV that satisfy a tumor-to-blood ratio (T/B) greater than 1.2. FDG and FMISO lesions were co-registered, and a voxel-by-voxel correlation between the two datasets was performed. FDG and FMISO TVs' SUVs were also compared as well as the intra-tumoral homogeneity of the two radiotracers. Separate analysis was performed for the primary tumors and LNs. RESULTS: Twenty-six percent of the primary tumors and 15% of LNs showed a strong correlation (R > 0.7) between FDG and FMISO intra-tumor distributions when considering the MTV. For the HV, only 19% of primary tumors and 12% of LN were strongly correlated. A weak and moderate correlation existed between the two markers SUVavg, and SUVmax in the case of the primary tumors, respectively. However, this was not the case for the LNs. Good concordances were also observed between the primary tumor's and LNs HV SUVavgs as well as between the corresponding hypoxic fractions (HF's). CONCLUSIONS: A moderate correlation between FDG and hypoxia radiotracer distribution, as measured by FMISO, seems to exist for primary tumors. However, discordant results were found in the case of LNs. Hypoxia appears to be the dominant driver of high FDG uptake in selected tumors only, and therefore FDG PET images cannot be used as a universal surrogate to identify or predict intra-tumor hypoxia.

A study of 18F-FLT positron emission tomography/computed tomography imaging in cases of prefibrotic/early primary myelofibrosis and essential thrombocythemia.

The objectives of this research project are to study in patients with primary myelofibrosis (PMF) and Essential Thrombocythemia (ET); (1) the uptake patterns of FLT-PET (FLT-PET) and its value in diagnosing, staging, and treatment response monitoring of malignant hematopoiesis, (2) compare imaging findings from FLT-PET with bone marrow biopsy (standard of care), and (3) associate FLT-PET uptake patterns with genetic makeup such as JAK2 (Janus kinase 2), CALR (Calreticulin), MPL (myeloproliferative leukemia protein), Triple negative disease, and allele burden.This trial is registered in ClinicalTrials.gov with number NCT03116542. Protocol version: Mar 2017.

A pilot study of 13N-ammonia cardiac PET imaging to assess subacute cardiotoxicity following adjuvant intensity-modulated radiotherapy for locally advanced breast cancer.

OBJECTIVE: (1) Assess the feasibility of 13 N-ammonia cardiac PET (13 N-ammonia-PET) imaging in radiotherapy (RT) treatment position in locally-advanced breast cancer (LABC) patients. (2) Correlate pre-/post-RT changes in myocardial flow reserve (MFR) with the corresponding radiation heart dose. METHODS: Ten left-sided LABC patients undergoing Volumetric Modulated-Arc-Therapy (VMAT) to chest wall and regional lymph nodes underwent a rest/stress 13 N-ammonia-PET at baseline and (median) 13 months post-RT. Changes in cardiac functions and coronary artery Ca2+ scoring between baseline and follow-up were correlated with average RT dose to the myocardium,3 coronary territories, and 17 myocardial segments. RESULTS: Eight (of 10) patients successfully completed the study. The average rest (stress) global MBF (ml.g-1.min-1) for baseline (follow-up) were 0.83 ± 0.25 (2.4 ± 0.79) and 0.92 ± 0.30 (2.76 ± 0.71), respectively. Differences in MBF, heart rate, blood pressure, and rate-pressure product (RPP) between baseline and follow-up were insignificant (P > 0.1).Strong (R = 0.79; P < 0.01) and moderate (R = 0.53; P = 0.37) correlation existed between MBF Rest and MBF Stress, and RPP respectively. Four patients showed a reduction in MFR of up to ~41% in follow-up studies, increasing to ~52% in myocardial segments close to high-radiation isodose lines in 5/8 patients. Agatston Ca + 2 scoring were zero in both baseline and follow-up in six patients; two patients exhibited mild increase in Ca + 2 on follow-ups (range:10-20).Rest and stress LVEF's were normal (>50) for all patients in both studies. CONCLUSION: The feasibility of 13 N-ammonia-PET imaging in treatment position of LABC patients was demonstrated. MFR at 1-year post-irradiation of the heart decreased in 50% of the patients. MFR may be a potential index for early detection of cardiotoxicity in BC patients receiving RT to the chest wall.

Physical performance of a long axial field-of-view PET scanner prototype with sparse rings configuration: A Monte Carlo simulation study.

PURPOSE: There is a growing interest in extending the axial fields-of-view (AFOV) of PET scanners. One major limitation for the widespread clinical adoption of such systems is the multifold increase in the associated material costs. In this study, we propose a cost-effective solution to extend the PET AFOV using a sparse detector rings configuration. The corresponding physical performance was validated using Monte Carlo simulations. METHODS: Monte Carlo model of the Siemens BiographTM mCT PET/CT, with a 21.8 cm AFOV and a set of compact rings of LSO crystals was developed as a gold standard. The mCT configuration was then modified by interleaving the LSO crystals in the axial direction within each detector block with 4 mm physical gaps (equivalent to the LSO crystal axial dimension) thus extending the AFOV to 43.6 cm (Ex-mCT). The physical performances of the two MC models were assessed and then compared using NEMA NU 2-2007 standards. RESULTS: Ex-mCT showed <0.2 mm difference in transaxial spatial resolution, and, 0.8 mm and 0.3 mm deterioration in axial spatial resolution, compared to the mCT, at 1 and 10 cm off-center of the transaxial field-of-view respectively. The system sensitivities for the mCT and Ex-mCT models were 9.4 ± 0.2 and 10.75 ± 0.2 cps/kBq respectively. The higher sensitivity of Ex-mCT was due to four additional detector rings required to double the mCT AFOV. PET images of the NEMA Image Quality (IQ) phantom showed no artifacts due to detector rings sparsity, and all spheres were visible in both configurations. Ex-mCT achieved percent contrast recoveries within 5.6% of those of the mCT for all spheres and a maximum of 36% higher background variability at the center of the AFOV. The Ex-mCT, however, showed a more uniform noise distribution over an axial range of almost twice the length of the mCT AFOV. CONCLUSIONS: Using the proposed sparse detector-ring configuration, the AFOV of current generation PET systems can be doubled while maintaining the original number and volume of detector crystal elements, and without jeopardizing the system's overall physical performance. Despite an increase in the noise level, the Ex-mCT exhibited an improved noise uniformity.

Inter-operator variability in compartmental kinetic analysis of 18F-fluoromisonidazole dynamic PET.

PURPOSE: To assess the inter-operator variability in compartment analysis (CA) of dynamic-FMISO (dyn-FMISO) PET. METHODS: Study-I: Five investigators conducted CA for 23 NSCLC dyn-FMISO tumor time-activity-curves. Study-II: Four operators performed CA for four NSCLC dyn-FMISO datasets. Repeatability of Kinetic-Rate-Constants (KRCs) was assessed. RESULTS: Study-I: Strong correlation (ICC > 0.9) and interchangeable results among operators existed for all KRCs. Study-II: Up to 103% variability in tumor segmentation, and weaker ICC in KRCs (ICC-VB = 0.53; ICC-K1 = 0.91; ICC-K1/k2 = 0.25; ICC-k3 = 0.32; ICC-Ki = 0.54) existed. All KRCs were repeatable among the different operators. CONCLUSIONS: Inter-operator variability in CA of dyn-FMISO was shown to be within statistical errors.

Pharmacokinetic Analysis of Dynamic 18F-Fluoromisonidazole PET Data in Non-Small Cell Lung Cancer.

Hypoxic tumors exhibit increased resistance to radiation, chemical, and immune therapies. 18F-fluoromisonidazole (18F-FMISO) PET is a noninvasive, quantitative imaging technique used to evaluate the magnitude and spatial distribution of tumor hypoxia. In this study, pharmacokinetic analysis (PKA) of 18F-FMISO dynamic PET extended to 3 h after injection is reported for the first time, to our knowledge, in stage III-IV non-small cell lung cancer (NSCLC) patients. Methods: Sixteen patients diagnosed with NSCLC underwent 2 PET/CT scans (1-3 d apart) before radiation therapy: a 3-min static 18 F-FDG and a dynamic 18F-FMISO scan lasting 168 ± 15 min. The latter data were acquired in 3 serial PET/CT dynamic imaging sessions, registered with each other and analyzed using pharmacokinetic modeling software. PKA was performed using a 2-tissue, 3-compartment irreversible model, and kinetic parameters were estimated for the volumes of interest determined using coregistered 18F-FDG images for both the volume of interest-averaged and the voxelwise time-activity curves for each patient's lesions, normal lung, and muscle. Results: We derived average values of 18F-FMISO kinetic parameters for NSCLC lesions as well as for normal lung and muscle. We also investigated the correlation between the trapping rate (k3) and delivery rate (K1), influx rate (Ki ) constants, and tissue-to-blood activity concentration ratios (TBRs) for all tissues. Lesions had trapping rates 1.6 times larger, on average, than those of normal lung and 4.4 times larger than those in muscle. Additionally, for almost all cases, k3 and Ki had a significant strong correlation for all tissue types. The TBR-k3 correlation was less straightforward, showing a moderate to strong correlation for only 41% of lesions. Finally, K1-k3 voxelwise correlations for tumors were varied, but negative for 76% of lesions, globally exhibiting a weak inverse relationship (average R = -0.23 ± 0.39). However, both normal tissue types exhibited significant positive correlations for more than 60% of patients, with 41% having moderate to strong correlations (R > 0.5). Conclusion: All lesions showed distinct 18F-FMISO uptake. Variable 18F-FMISO delivery was observed across lesions, as indicated by the variable values of the kinetic rate constant K1 Except for 3 cases, some degree of hypoxia was apparent in all lesions based on their nonzero k3 values.

Reproducibility of 18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer.

BACKGROUND: Hypoxic tumours exhibit increased resistance to radiation, chemical, and immune therapies. 18F-fluoromisonidazole (FMISO) positron emission tomography (PET) is a non-invasive, quantitative imaging technique used to evaluate the presence and spatial distribution of tumour hypoxia. To facilitate the use of FMISO PET for identification of individuals likely to benefit from hypoxia-targeted treatments, we investigated the reproducibility of FMISO PET spatiotemporal intratumour distribution in patients with non-small cell lung cancer (NSCLC). METHODS: Ten patients underwent 18F-fluorodeoxyglucose (FDG) PET/CT scans, followed by two FMISO PET/CT scans 1-2 days apart. Nineteen lesions in total were segmented from co-registered FDG PET image sets. Volumes of interest were also defined on normal contralateral lung and subscapularis muscle. The Pearson correlation coefficient r was calculated for mean standardized uptake values (SUV) within investigated volumes of interest and for voxels within tumour volumes (r TV). The reproducibility of FMISO voxelwise distribution, SUV- and tumour-to-blood ratio (TBR)-derived indices was assessed using correlation and Bland-Altman analyses. RESULTS: The SUVmax, SUVmean, TBRmax, and TBRmean were highly correlated (r ≥ 0.87, p < 0.001) and were reproducible to within 10-15 %. The mean r TV was 0.84 ± 0.10. 77 % of voxels identified as hypoxic on one FMISO scan were confirmed as such on the other FMISO scan. Mean voxelwise differences between TBR values as calculated from pooled data including all lesions were 0.9 ± 10.8 %. CONCLUSIONS: High reproducibility of FMISO intratumour distribution in NSCLC patients was observed, facilitating its use in determining the topology of the hypoxic tumour sub-volumes for dose escalation, in patient stratification strategies for hypoxia-targeted therapies, and in monitoring response to therapeutic interventions. TRIAL REGISTRATION: Current Controlled Trials NCT02016872.

Feasibility of 18F-Fluoromisonidazole Kinetic Modeling in Head and Neck Cancer Using Shortened Acquisition Times.

UNLABELLED: (18)F-fluoromisonidazole dynamic PET (dPET) is used to identify tumor hypoxia noninvasively. Its routine clinical implementation, however, has been hampered by the long acquisition times required. We investigated the feasibility of kinetic modeling using shortened acquisition times in (18)F-fluoromisonidazole dPET, with the goal of expediting the clinical implementation of (18)F-fluoromisonidazole dPET protocols. METHODS: Six patients with squamous cell carcinoma of the head and neck and 10 HT29 colorectal carcinoma-bearing nude rats were studied. In addition to an (18)F-FDG PET scan, each patient underwent a 45-min (18)F-fluoromisonidazole dPET scan, followed by 10-min acquisitions at 96 ± 4 and 163 ± 17 min after injection. Ninety-minute (18)F-fluoromisonidazole dPET scans were acquired in animals. Intratumor voxels were classified into 4 clusters based on their kinetic behavior using k-means clustering. Kinetic modeling was performed using the foregoing full datasets (FD) and repeated for each of 2 shortened datasets corresponding to the first approximately 100 min (SD1; patients only) or the first 45 min (SD2) of dPET data. The kinetic rate constants (KRCs) as calculated with a 2-compartment model for both SD1 and SD2 were compared with those derived from FD by correlation (Pearson), regression (Passing-Bablok), deviation (Bland-Altman), and classification (area-under-the-receiver-operating characteristic curve) analyses. Simulations were performed to assess uncertainties due to statistical noise. RESULTS: Strong correlation (r ≥ 0.75, P < 0.001) existed between all KRCs deduced from both SD1 and SD2, and from FD. Significant differences between KRCs were found only for FD-SD2 correlations in patient studies. K1 and k3 were reproducible to within approximately 6% and approximately 30% (FD-SD1; patients) and approximately 4% and approximately 75% (FD-SD2; animals). Area-under-the-receiver-operating characteristic curve values for classification of patient clusters as hypoxic, using a tumor-to-blood ratio greater than 1.2, were 0.91 (SD1) and 0.86 (SD2). The percentage SD in estimating K1 and k3 from 45-min shortened datasets due to noise was less than 1% and between 2% and 12%, respectively. CONCLUSION: Using single-session 45-min shortened (18)F-fluoromisonidazole dPET datasets appears to be adequate for the identification of intratumor regions of hypoxia. However, k3 was significantly overestimated in the clinical cohort. Further studies are necessary to evaluate the clinical significance of differences between the results as calculated from full and shortened datasets.

Respiratory Motion Correction Strategies in Thoracic PET-CT Imaging.

PET-CT scanners allow robust and synergistic fusion of anatomic and functional information, which has improved sensitivity, specificity, and enhancement in the value of PET and CT when assessing tumor response to therapy. Breathing motion and the difference in time resolutions commonly cause motion artifacts and spatial mismatch between the corresponding image sets. Correction for the breathing-induced artifacts represents a particular challenge. This article summarizes the materials, methods, and results involved in multiple investigations of the correction for respiratory motion in PET-CT imaging of the thorax. Some methods use respiratory-phase data selection, whereas others have adopted sophisticated software techniques.

Recurrent non-small cell lung cancer: evaluation of CT-guided radiofrequency ablation as salvage therapy.

BACKGROUND: Radiofrequency ablation (RFA) is a potential application as a salvage tool after failure of surgery, chemotherapy, or radiotherapy of non-small cell lung cancer (NSCLC). Although several studies have evaluated the use of RFA in primary NSCLC, there is little literature on its potential application as a salvage tool. PURPOSE: To evaluate CT-guided RFA employed as a salvage therapy for pulmonary recurrences of NSCLC after prior treatment with chemotherapy, radiation therapy, and/or surgery. MATERIAL AND METHODS: A retrospective computer database search yielded 33 patients with biopsy proven primary NSCLC who underwent CT-guided RFA of 39 recurrent tumors following surgery, chemotherapy, and/or radiotherapy. Follow-up imaging was performed with CT and PET-CT. The endpoints of interest were progression-free survival (PFS) and time to local progression (TTLP). PFS and TTLP were compared by lesion size (<3 cm, ≥3 cm). RESULTS: The median PFS was 8 months. For patients with a tumor size <3 cm median PFS was 11 months, whereas the median PFS of patients with a tumor size ≥3 cm was 5 months. The difference did not reach statistical significance (P = 0.09). The median TTLP of all tumors was 14 months. TTLP of ablated tumors <3 cm in size was 24 months, compared to 8 months for ablated tumors ≥3 cm in size. The difference did not reach statistical significance (P = 0.07). CONCLUSION: RFA of recurrent NSCLC may be a valuable salvage tool to achieve local tumor control, especially in tumors measuring <3 cm in size.

Radiofrequency ablation of non-small-cell carcinoma of the lung under real-time FDG PET CT guidance.

Radiofrequency ablation (RFA) is a well-established method in treatment of patients with lung carcinomas who are not candidates for surgical resection. Usually computed tomographic (CT) guidance is used for the procedure, thus enabling needle placement and permitting evaluation of complications such as pneumothorax and bleeding. (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is generally used for tumor activity assessment and is therefore useful in follow-up after tumor treatment. A method that provides real-time image-based monitoring of RFA to ensure complete tumor ablation would be a valuable tool. In this report, we describe the behavior of preinjected FDG during PET CT-guided RFA of a non-small-cell lung carcinoma and discuss the value of FDG as a tool to provide intraprocedure monitor ablation. The size and the form of the activity changed during ablation. Ablation led to increase of the size and blurring and irregularity of the contour compared to pretreatment imaging. The maximal standardized uptake value decreased only slightly during the procedure. Therefore, before RFA, FDG PET can guide initial needle placement, but it does not serve as a monitoring tool to evaluate residual viable tissue during the procedure.

Modeling acute and chronic hypoxia using serial images of 18F-FMISO PET.

PURPOSE: Two types of tumor hypoxia most likely exist in human cancers: Chronic hypoxia due to the paucity of blood capillaries and acute hypoxia due to temporary shutdoWn of microvasculatures or fluctuation in the red cell flux. In a recent hypoxia imaging study using 18F-FMISO PET, the authors observed variation in tracer uptake in two sequential images and hypothesized that variation in acute hypoxia may be the cause. In this study, they develop an iterative optimization method to delineate chronic and acute hypoxia based on the 18F-FMISO PET serial images. METHODS: They assume that (1) chronic hypoxia is the same in the two scans and can be represented by a Gaussian distribution, while (2) acute hypoxia varies in the two scans and can be represented by Poisson distributions. For validation, they used Monte Carlo simulations to generate pairs of 18F-FMISO PET images with known proportion of chronic and acute hypoxia and then applied the optimization method to the simulated serial images, yielding excellent fit between the input and the fitted results. They then applied this method to the serial 18F-FMISO PET images of 14 patients with head and neck cancers. RESULTS: The results show good fit of the chronic hypoxia to Gaussian distributions for 13 out of 14 patients (with R2>0.7). Similarly, acute hypoxia appears to be well described by the Poisson distribution (R2>0.7) with three exceptions. The model calculation yielded the amount of acute hypoxia, which differed among the patients, ranging from approximately 13% to 52%, with an average of approximately 34%. CONCLUSIONS: This is the first effort to separate acute and chronic hypoxia from serial PET images of cancer patients.

Evaluation of a compartmental model for estimating tumor hypoxia via FMISO dynamic PET imaging.

This paper systematically evaluates a pharmacokinetic compartmental model for identifying tumor hypoxia using dynamic positron emission tomography (PET) imaging with 18F-fluoromisonidazole (FMISO). A generic irreversible one-plasma two-tissue compartmental model was used. A dynamic PET image dataset was simulated with three tumor regions-normoxic, hypoxic and necrotic-embedded in a normal-tissue background, and with an image-based arterial input function. Each voxelized tissue's time activity curve (TAC) was simulated with typical values of kinetic parameters, as deduced from FMISO-PET data from nine head-and-neck cancer patients. The dynamic dataset was first produced without any statistical noise to ensure that correct kinetic parameters were reproducible. Next, to investigate the stability of kinetic parameter estimation in the presence of noise, 1000 noisy samples of the dynamic dataset were generated, from which 1000 noisy estimates of kinetic parameters were calculated and used to estimate the sample mean and covariance matrix. It is found that a more peaked input function gave less variation in various kinetic parameters, and the variation of kinetic parameters could also be reduced by two region-of-interest averaging techniques. To further investigate how bias in the arterial input function affected the kinetic parameter estimation, a shift error was introduced in the peak amplitude and peak location of the input TAC, and the bias of various kinetic parameters calculated. In summary, mathematical phantom studies have been used to determine the statistical accuracy and precision of model-based kinetic analysis, which helps to validate this analysis and provides guidance in planning clinical dynamic FMISO-PET studies.

Evaluation of different methods of 18F-FDG-PET target volume delineation in the radiotherapy of head and neck cancer.

OBJECTIVE: To quantify differences between the alternative methods of F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)-based delineation of the gross tumor volume in patients with head and neck cancer. MATERIALS AND METHODS: Twelve patients with locally-advanced head and neck carcinomas were studied. The reference gross tumor volume (GTVref) was established by a radiation oncologist, along with a neuroradiologist, using the computed tomography-simulation and diagnostic magnetic resonance imaging data. With the GTVref obscured, a second radiation oncologist and a nuclear medicine physician determined the following contours: (1) high FDG uptake based on visual inspection (GTVvis), (2) the contour derived from the 50% maximum standardized uptake value (SUV) threshold (GTV50), (3) the contour derived from a 2.5 SUV absolute threshold (GTV2.5), and (4) the contours derived from an iterative segmentation algorithm (GTViter). These volumes were compared with the GTVref using a signed-ranks test with the exact reference distribution. RESULTS: The average GTVref was 75.5 mL (median 72.8 mL, range 22.2-138.4 mL). The average GTVvis was 57.6 (median 55.4 mL, range 12-115.8 mL). Overall, a 21% reduction in volume size was observed with GTVvis versus GTVref. When the signed-ranks test with the exact reference distribution was applied, the difference was not statistically significant (P = 0.32). The average GTV2.5 was 60 mL (median 64.5, range 8.8-90.3 mL). The differences between GTV2.5 and GTVref were not statistically significant (P = 0.35). The use of GTV50 and GTViter produced significantly smaller volumes with respect to GTVref (P < 0.005). CONCLUSIONS: PET-based tumor volumes are strongly affected by the choice of threshold level. Quantitatively, GTVs derived from visual inspection of the region of high FDG uptake do not significantly differ from GTVref in this cohort of patients. The inclusion of alternative FDG-PET segmentation data, other than visual inspection, may reduce target volumes significantly.

Respiratory motion in positron emission tomography/computed tomography: a review.

The development of positron emission tomography/computed tomography (PET/CT) scanners has allowed not only straightforward but also synergistic fusion of anatomical and functional information. Combined PET/CT imaging yields an increased sensitivity and specificity beyond that which either of the 2 modalities possesses separately and therefore provides improved diagnostic accuracy. Because attenuation correction in PET is performed with the use of CT images, with CT used in the localization of disease, accurate spatial registration of PET and CT image sets is required. Correcting for the spatial mismatch caused by respiratory motion represents a particular challenge for the requisite registration accuracy as a result of differences in temporal resolution between the 2 modalities. This review provides a brief summary of the materials, methods, and results involved in multiple investigations of the correction for respiratory motion in PET/CT imaging of the thorax, with the goal of improving image quality and quantitation. Although some schemes use respiratory-phase data selection to exclude motion artifacts, others have adopted sophisticated software techniques. The various image artifacts associated with breathing motion are also described.