Real-time Positron Emission Tomography Research Articles

Demonstration of real-time positron emission tomography biology-guided radiotherapy delivery to targets.

Biology-guided radiotherapy (BgRT) is a novel technology that uses positron emission tomography (PET) data to direct radiotherapy delivery in real-time. BgRT enables the precise delivery of radiation doses based on the PET signals emanating from PET-avid tumors on the fly. In this way, BgRT uniquely utilizes radiotracer uptake as a biological beacon for controlling and adjusting dose delivery in real-time to account for target motion. To demonstrate using real-time PET for BgRT delivery on the RefleXion X1 radiotherapy machine. The X1 radiotherapy machine is a rotating ring-gantry radiotherapy system that generates a nominal 6MV photon beam, PET, and computed tomography (CT) components. The system utilizes emitted photons from PET-avid targets to deliver effective radiation beamlets or pulses to the tumor in real-time. This study demonstrated a real-time PET BgRT delivery experiment under three scenarios. These scenarios included BgRT delivering to (S1 ) a static target in a homogeneous and heterogeneous environment, (S2 ) a static target with a hot avoidance structure and partial PET-avid target, and (S3 ) a moving target. The first step was to create stereotactic body radiotherapy (SBRT) and BgRT plans (offline PET data supported) using RefleXion's custom-built treatment planning system (TPS). Additionally, to create a BgRT plan using PET-guided delivery, the targets were filled with 18F-Fluorodeoxyglucose (FDG), which represents a tumor/target, that is, PET-avid. The background materials were created in the insert with homogeneous water medium (for S1 ) and heterogeneous water with styrofoam mesh medium. A heterogeneous background medium simulated soft tissue surrounding the tumor. The treatment plan was then delivered to the experimental setups using a pre-commercial version of the X1 machine. As a final step, the dosimetric accuracy for S1 and S2 was assessed using the ArcCheck analysis tool-the gamma criteria of 3%/3mm. For S3 , the delivery dose was quantified using EBT-XD radiochromic film. The accuracy criteria were based on coverage, where 100% of the clinical target volume (CTV) receives at least 97% of the prescription dose, and the maximum dose in the CTV was ≤130% of the maximum planned dose (97%≤CTV≤130%). For the S1, both SBRT and BgRT deliveries had gamma pass rates greater than 95% (SBRT range: 96.9%-100%, BgRT range: 95.2%-98.9%), while in S2 , the gamma pass rate was 98% for SBRT and between 95.2% and 98.9% for BgRT plan delivering. For S3 , both SBRT and BgRT motion deliveries met CTV dose coverage requirements, with BgRT plans delivering a very high dose to the target. The CTV dose ranges were (a) SBRT:100.4%-120.4%, and (b) BgRT: 121.3%-139.9%. This phantom-based study demonstrated that PET signals from PET-avid tumors can be utilized to direct real-time dose delivery to the tumor accurately, which is comparable to the dosimetric accuracy of SBRT. Furthermore, BgRT delivered a PET-signal controlled dose to the moving target, equivalent to the dose distribution to the static target. A future study will compare the performance of BgRT with conventional image-guided radiotherapy.

BIOGUIDE-X: A First-in-Human Study of the Performance of Positron Emission Tomography-Guided Radiation Therapy

Positron emission tomography (PET)-guided radiation therapy is a novel tracked dose delivery modality that uses real-time PET to guide radiation therapy beamlets. The BIOGUIDE-X study was performed with sequential cohorts of participants to (1) identify the fluorodeoxyglucose (FDG) dose for PET-guided therapy and (2) confirm that the emulated dose distribution was consistent with a physician-approved radiation therapy plan. This prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (2-5 cm) in the lung or bone. For cohort I, a modified 3 + 3 design was used to determine the FDG dose that would result in adequate signal for PET-guided therapy. For cohort II, PET imaging data were collected on the X1 system before the first and last fractions among patients undergoing conventional stereotactic body radiation therapy. PET-guided therapy dose distributions were modeled on the patient's computed tomography anatomy using the collected PET data at each fraction as input to an "emulated delivery" and compared with the physician-approved plan. Cohort I demonstrated adequate FDG activity in 6 of 6 evaluable participants (100.0%) with the first injected dose level of 15 mCi FDG. In cohort II, 4 patients with lung tumors and 5 with bone tumors were enrolled, and evaluable emulated delivery data points were collected for 17 treatment fractions. Sixteen of the 17 emulated deliveries resulted in dose distributions that were accurate with respect to the approved PET-guided therapy plan. The 17th data point was just below the 95% threshold for accuracy (dose-volume histogram score = 94.6%). All emulated fluences were physically deliverable. No toxicities were attributed to multiple FDG administrations. PET-guided therapy is a novel radiation therapy modality in which a radiolabeled tumor can act as its own fiducial for radiation therapy targeting. Emulated therapy dose distributions calculated from continuously acquired real-time PET data were accurate and machine-deliverable in tumors that were 2 to 5 cm in size with adequate FDG signal characteristics.

Positron emission tomography dataset of [11C]carbon dioxide storage in coal for geo-sequestration application

Positron Emission Tomography (PET) imaging has demonstrated its capability in providing time-lapse fluid flow visualisation for improving the understanding of flow properties of geologic media. To investigate the process of CO2 geo-sequestration using PET imaging technology, [11C]CO2 is the most optimal and direct radiotracer. However, it has not been extensively used due to the short half-life of Carbon-11 (20.4 minutes). In this work, a novel laboratory protocol is developed to use [11C]CO2 as radiolabelled tracer to visualise and quantify in-situ CO2 adsorption, spreading, diffusion, and advection flow in coal. This protocol consists of generation and delivering of [11C]CO2, lab-based PET scanning, subsequent micro-CT scanning, and data processing. The lab-based PET scanning setup integrates in-situ core flooding tests with PET scanning. The real-time PET images are acquired under different storage conditions, including early gas production stage, depleted stage, and late storage stage. These datasets can be used to study across-scale theoretical and experimental study of CO2 flow behaviour in coal with the application to CO2 geo-sequestration.

Imaging Performance of the PET Scan on a Novel Ring Gantry-Based PET/CT Linear Accelerator System in the First-in-Human Study of Biology-Guided Radiotherapy

Biology-guided radiotherapy (BgRT) is a novel tracked dose delivery modality using real-time positron emission tomography (PET) to guide radiotherapy beamlets. The present study was performed with sequential cohorts of participants to evaluate the performance and safety of BgRT. Primary endpoints were previously reported. We hereby report on one of the secondary endpoints assessing a novel treatment planning machine with integrated dual kVCT/PET imaging ("novel device") performance in comparison to a third-party diagnostic PET/CT scan. This single-arm, open-label, prospective study included participants with at least 1 FDG-avid targetable primary or metastatic tumor (≥2cm and ≤5cm) in the lung or bone. PET imaging data were collected on the novel device and on a third-party diagnostic PET/CT performed in sequence once at the planning timepoint in Cohort I, and immediately before the last fraction among patients undergoing stereotactic radiotherapy in Cohort II. Three central read radiation oncologists (CRRO) provided an interpretation of the novel device PET scans which were compared to an agreement standard based on 3 central radiologists' review of the paired diagnostic PET/CT scan. Positive percent agreement for localization of the target tumor within the biology-tracking zone (BTZ) was the key metric because it reflects whether advancing patients to subsequent steps in the BgRT workflow based on the novel device's imaging was ultimately appropriate. In Cohort 1, 6 image comparisons were performed. The positive (%) agreement for the aggregate radiation oncologist review was 100% (5/5), reflecting that in all 5 cases where the aggregate radiation oncologists deemed the tumor to fall within the BTZ based upon the novel device PET images, the central radiologists came to the same conclusion upon review of the paired diagnostic PET/CT images. The overall (%) agreement for the aggregate radiation oncologist review was 83.3% (5/6): localization was not established on the novel device in 1 case, even though it was established on the diagnostic PET/CT. This would not pose risk in real world practice as BgRT candidacy would be aborted for tumors not visible on the novel device. In Cohort II, among the 7 image comparisons, there was 100% positive percent agreement between the aggregate CRRO and the agreement standard as the localization criteria was met in both scans for all 7 patients. This was concordant with a 100% overall percent agreement. This investigation demonstrated a 100% positive percent agreement between central review of this novel device images by radiation oncologists and central review of the accompanying third-party PET/CT images by radiologists. There were no cases where a positive localization by the aggregate CRRO was not confirmed by the third-party PET/CT standard, providing evidence against the likelihood of falsely positive localizations on the novel device that would inappropriately advance patients in the workflow.

Clinical characteristics of patients with non-small cell lung cancer eligible for biology-guided radiotherapy.

e20523 Background: Biology-guided radiotherapy (BgRT) is a novel radiotherapy modality that uses real-time positron emission tomography (PET) to guide radiotherapy beamlets. BgRT recently received FDA clearance for clinical use using the 18F FDG radiotracer for the treatment of tumors in lung and bone. We sought to identify non-small cell lung cancer (NSCLC) patients who may be candidates for BgRT based on diagnostic FDG PET/CT imaging. Methods: We conducted an IRB-approved retrospective assessment of NSCLC patients diagnosed between 01/01/2006 and 12/31/2013 at a tertiary care center in the United States. Patient and tumor characteristics were verified by an institutional data repository team and through electronic medical record review. Patients were excluded from analysis when documentation of clinical/ imaging findings was insufficient. Frequency of characteristics were interpreted with and without tumor diameter and maximum standardized uptake value (SUVMax) parameters, to confirm eligibility for BgRT on this novel radiotherapy device. Results: Of the 686 patients eligible for analysis, 523 presented with tumor SUVMax of ≥6 on diagnostic PET imaging and 360 presented with tumor diameters of at least 2 cm and below 5 cm. Of the 277 patients who met both SUVMax and size parameters, respectively, 75 (27.1%), 145 (52.3%), and 57 (20.6%) presented with squamous, adenocarcinoma, or other/unknown histology, and 77 (27.9%), 29 (10.5%), 92 (33.3%), and 78 (28.3%) presented with stage I, II, III, or IV tumors (AJCC 7th edition). Conclusions: Theoretical applicability of biology-guided radiotherapy was observed in our NSCLC patient cohort. Therefore, despite current limitations of radiotracer uptake thresholds and tumor size restrictions, there is broad potential applicability of this treatment modality, either as a single modality treatment or in conjunction with active systemic therapy. [Table: see text]

Eligibility of patients with esophageal and gastroesophageal cancer for biology-guided radiotherapy in a retrospective cohort.

e16100 Background: Biology-guided radiotherapy (BgRT) is a novel radiotherapy modality that uses real-time positron emission tomography (PET) to guide radiotherapy beamlets. The FDA recently cleared BgRT for clinical use for tumors in lung and bone using 18F FDG radiotracer. We sought to identify esophageal cancer (EC) and gastroesophageal junction cancer (GEJC) patients who may be BgRT candidates based on diagnostic FDG PET/CT imaging. Methods: Through IRB-approved extraction of patient medical record data from an institutional repository of prospectively maintained data, we verified a database of EC and GEJC patients diagnosed at a US tertiary care center between 01/01/2006 and 12/31/2013. When insufficient diagnostic clinical information was present, patients were excluded. Patient and tumor qualities were quantified and subjected to parameters of tumor diameter (≥2cm, <5cm) and maximum standardized uptake value (≥6) to observe potential characteristics of a patient population eligible for this novel BgRT mechanism. Results: Thirty patients met tumor size and FDG uptake criteria for BgRT therapy out of an overall patient cohort of 90 patients. A significantly greater proportion of patients within the BgRT-eligible cohort presented with esophageal tumors (83.3%) compared to non-eligible patients (58.3%, P=0.0177). Otherwise, there was no significant variation of patient sex, race, tumor histology, tumor stage, comorbidity score, and pre-treatment weight loss between patients eligible and not eligible for BgRT therapy. Conclusions: After applying current boundaries of tumor size and radiotracer uptake for effective BgRT intervention, we observed broad applicability of the novel treatment modality across EC/ GEJC patients of varying characteristics and tumor qualities. The high eligibility of patients with tumors located within the esophagus supports further investigation of BgRT in their management. [Table: see text]

Real-Time PET Imaging for Range Verification of Helium Radiotherapy

Real-time range verification of particle beams is important for optimal exploitation of the tissue-sparing advantages of particle therapy. Positron Emission Tomography (PET) of the beam-induced positron emitters such as 15O (T1/2 = 122 s) and 11C (T1/2 = 1223 s) has been used for monitoring of therapy in both clinical and preclinical studies. However, the half-lives of these nuclides preclude prompt feedback, i.e., on a sub-second timescale, on dose delivery. The in vivo verification technique relying on the in-beam PET imaging of very short-lived positron emitters such as 12N (T1/2 = 11 ms), recently proposed and investigated in feasibility experiments with a proton beam, provides millimeter precision in range measurement a few tens of milliseconds after the start of an irradiation. With the increasing interest in helium therapy, it becomes relevant to study the feasibility of prompt feedback using PET also for helium beams. A recent study has demonstrated the production of very short-lived nuclides (T1/2 = 10 ms attributed to 12N and/or 13O) during irradiation of water and graphite with helium ions. This work is aimed at investigating the range verification potential of imaging these very short-lived nuclides. PMMA targets were irradiated with a 90 AMeV 4He pencil beam consisting of a series of pulses of 10 ms beam-on and 90 ms beam-off. Two modules of a modified Siemens Biograph mCT PET scanner (21 × 21 cm2), installed 25 cm apart, were used to image the beam-induced PET activity during the beam-off periods. For the irradiation of PMMA, we identify the very short-lived activity earlier observed to be 12N (T1/2 = 11.0 ms). The range precision determined from the 12N activity profile that is measured after just one beam pulse was found to be 9.0 and 4.1 mm (1σ) with 1.3 × 1074He ions per pulse and 6.6 × 1074He ions per pulse, respectively. When considering 4.0 × 1074He ions, which is about the intensity of the most intense distal layer spot in a helium therapy plan, a range verification precision in PMMA of 5.7 mm (1σ) can be realized. The range precision scales approximately with the inverse square root of the number of 4He ions, i.e., the relative statistical accuracy of the number of coincidence events. Thus, when summing data over about 10 distal layer spots, this study shows good prospects for obtaining 1.8 mm (1σ) precision in range verification, within 50 ms after the start of a helium irradiation by in-beam PET imaging (scanner 29% solid angle) of 12N.

Real-Time 3D PET Image with Pseudoinverse Reconstruction

Real-time positron emission tomography (PET) may provide information from first-shot images, enable PET-guided biopsies, and allow awake animal studies. Fully-3D iterative reconstructions yield the best images in PET, but they are too slow for real-time imaging. Analytical methods such as Fourier back projection (FBP) are very fast, but yield images of poor quality with artifacts due to noise or data incompleteness. In this work, an image reconstruction based on the pseudoinverse of the system response matrix (SRM) is presented. w. To implement the pseudoinverse method, the reconstruction problem is separated into two stages. First, the axial part of the SRM is pseudo-inverted (PINV) to rebin the 3D data into 2D datasets. Then, the resulting 2D slices can be reconstructed with analytical methods or by applying the pseudoinverse algorithm again. The proposed two-step PINV reconstruction yielded good-quality images at a rate of several frames per second, compatible with real time applications. Furthermore, extremely fast direct PINV reconstruction of projections of the 3D image collapsed along specific directions can be implemented.

An FPGA-Based Real-Time Maximum Likelihood 3D Position Estimation for a Continuous Crystal PET Detector

For the continuous crystal-based positron emission tomography (PET) detector built in our lab, a maximum likelihood algorithm adapted for implementation on a field programmable gate array (FPGA) is proposed to estimate the three-dimensional (3D) coordinate of interaction position with the single-end detected scintillation light response. The row-sum and column-sum readout scheme organizes the 64 channels of photomultiplier (PMT) into eight row signals and eight column signals to be readout for X- and Y-coordinates estimation independently. By the reference events irradiated in a known oblique angle, the probability density function (PDF) for each depth-of-interaction (DOI) segment is generated, by which the reference events in perpendicular irradiation are assigned to DOI segments for generating the PDFs for X and Y estimation in each DOI layer. Evaluated by the experimental data, the algorithm achieves an average X resolution of 1.69 mm along the central $X$ -axis, and DOI resolution of 3.70 mm over the whole thickness (0–10 mm) of crystal. The performance improvements from 2D estimation to the 3D algorithm are also presented. Benefiting from abundant resources of FPGA and a hierarchical storage arrangement, the whole algorithm can be implemented into a middle-scale FPGA. By a parallel structure in pipelines, the 3D position estimator on the FPGA can achieve a processing throughput of 15 M events/s, which is sufficient for the requirement of real-time PET imaging.

Evolution of animal models in cancer vaccine development

Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide novel insight of host response. In conclusion, new feline models improve the predictive power of cancer immunotherapy and real-time PET imaging enables mechanistic monitoring of host immunity. Strategic utilization of these new tools will expedite cancer vaccine development.

64 Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques

Objective— A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used positron emission tomography (PET) and the novel PET ligand [ 64 Cu] [1,4,7,10-tetraazacyclododecane- N , N ′, N ″, N ‴-tetraacetic acid]- d -Phe1,Tyr3-octreotate ( 64 Cu-DOTATATE) to specifically target macrophages via the somatostatin receptor subtype-2 in vivo. Approach and Results— Ten patients underwent simultaneous PET/MRI to measure 64 Cu-DOTATATE uptake in carotid artery plaques before carotid endarterectomy. 64 Cu-DOTATATE uptake was significantly higher in symptomatic plaque versus the contralateral carotid artery ( P <0.001). Subsequently, a total of 62 plaque segments were assessed for gene expression of selected markers of plaque vulnerability using real-time quantitative polymerase chain reaction. These results were compared with in vivo 64 Cu-DOTATATE uptake calculated as the mean standardized uptake value. Univariate analysis of real-time quantitative polymerase chain reaction and PET showed that cluster of differentiation 163 (CD163) and CD68 gene expression correlated significantly but weakly with mean standardized uptake value in scans performed 85 minutes post injection ( P <0.001 and P =0.015, respectively). Subsequent multivariate analysis showed that CD163 correlated independently with 64 Cu-DOTATATE uptake ( P =0.031) whereas CD68 did not contribute significantly to the final model. Conclusions— The novel PET tracer 64 Cu-DOTATATE accumulates in atherosclerotic plaques of the carotid artery. CD163 gene expression correlated independently with 64 Cu-DOTATATE uptake measured by real-time quantitative polymerase chain reaction in the final multivariate model, indicating that 64 Cu-DOTATATE PET is detecting alternatively activated macrophages. This association could potentially improve noninvasive identification and characterization of vulnerable plaques.

A Real-Time Scintillation Crystal Identification Method and Its FPGA Implementation

At the expense of increasing the complexity, Zernike Moment (ZM) was used in Crystal Identification (CI) to solve the parallax error with the highest identification performance among recent methods that are based on Digital signal processing (DSP) algorithms. In Positron Emission Tomography (PET) scanners, the CI method must fulfill the real-time event rate processing that requires low complexity and fast algorithms. The main idea of this paper is the complexity reduction of the ZM-based CI method and using a Support Vector Machine (SVM) classifier to comply with the rate of real-time PET scanners. To achieve this goal, 1-D form of ZM and fast computations of cascaded ZM and SVM stages are proposed to minimize the complexity while preserving the highest performance among compared methods. The proposed fast ZM-SVM CI method is implemented using both MATLAB and FPGA and verified by identification of ~ 100 000 pulses of LSO-LuYAP scintillation crystals. The FPGA realization of the fast ZM-SVM CI method offers an identification rate of 90.6% at a rate of 6.2 Mevents/s using 16 samples per event which is sufficient for real time small animal PET scanners.

SU-E-J-215: Onboard Split PET Including the Effects of Attenuation, Scatter, and Random Events

Purpose: Positron emission tomography (PET) using split PET geometry was investigated as an on-board system for functional imaging and PET marker tracking, specifically with tomotherapy. The open dual ring PET would allow measurement of both inter and intra-fractional variation, improving the delineation of tumor volume at any stage in the radiation treatment delivery process. We present results from data obtained using Monte Carlo simulations including the effects of attenuation, random events, and scatter. Methods: PET design was accomplished via Monte Carlo simulations with GATE, the Geant4 Application for Emission Tomography. Images were reconstructed using Software for Image Reconstruction (STIR) with a fully 3D ordered subset expectation maximization (OSEM) image reconstruction technique. Results: Monte Carlo simulations of the split PET geometry indicate that including physical factors that degrade image quality such as attenuation, random events, and scatter still prove the feasibility of near real-time PET for both inter and intra-fractional radiation delivery. The image quality of scan times under 1 minute reveals that it is possible to utilize PET scanning and reconstruction during the treatment session intrafractionally. GATE also simulates the depth information but does not correct obliqueness of the path of line of response so the data is much moremore » realistic than the data obtained with ray tracing. Conclusion: Onboard split PET with TomoTherapy can generate quality images under 1 minute scan times without the need to correct for attenuation, scatter, random events, or depth information of the interaction.« less

Real-time FDG PET Guidance during Biopsies and Radiofrequency Ablation Using Multimodality Fusion with Electromagnetic Navigation

To assess the feasibility of combined electromagnetic device tracking and computed tomography (CT)/ultrasonography (US)/fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) fusion for real-time feedback during percutaneous and intraoperative biopsies and hepatic radiofrequency (RF) ablation. In this HIPAA-compliant, institutional review board-approved prospective study with written informed consent, 25 patients (17 men, eight women) underwent 33 percutaneous and three intraoperative biopsies of 36 FDG-avid targets between November 2007 and August 2010. One patient underwent biopsy and RF ablation of an FDG-avid hepatic focus. Targets demonstrated heterogeneous FDG uptake or were not well seen or were totally inapparent at conventional imaging. Preprocedural FDG PET scans were rigidly registered through a semiautomatic method to intraprocedural CT scans. Coaxial biopsy needle introducer tips and RF ablation electrode guider needle tips containing electromagnetic sensor coils were spatially tracked through an electromagnetic field generator. Real-time US scans were registered through a fiducial-based method, allowing US scans to be fused with intraprocedural CT and preacquired FDG PET scans. A visual display of US/CT image fusion with overlaid coregistered FDG PET targets was used for guidance; navigation software enabled real-time biopsy needle and needle electrode navigation and feedback. Successful fusion of real-time US to coregistered CT and FDG PET scans was achieved in all patients. Thirty-one of 36 biopsies were diagnostic (malignancy in 18 cases, benign processes in 13 cases). RF ablation resulted in resolution of targeted FDG avidity, with no local treatment failure during short follow-up (56 days). Combined electromagnetic device tracking and image fusion with real-time feedback may facilitate biopsies and ablations of focal FDG PET abnormalities that would be challenging with conventional image guidance.

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.

List-mode image reconstruction for real-time PET imaging

The problem of tomographic image reconstruction from measured projection data can be reduced to solving a set of linear equations represented in matrix form. In this paper, we show how image reconstruction in positron emission tomography (PET) can be achieved potentially in real-time using a regularized pseudo-inverse of the system matrix. An update of the current image estimate accounting for the next registered event can be obtained using a single column of the regularized pseudo-inverse matrix, thus allowing for instant visualization of the radioactivity distribution while the subject is still being scanned. The computed image estimate is the minimum-norm least-squares solution of the regularized inverse problem. The speed and performance of the algorithm were characterized and compared to those of a well-known statistical iterative algorithm. The proposed algorithm was validated with experimental list-mode PET data.

Real-time PET analysis of metastatic tumor cell trafficking in vivo and its relation to adhesion properties

Although a number of studies have indicated that highly metastatic cells tend to adhere more to target endothelium in vitro than low or non-metastatic cells, direct evidence about the correlation between cellular adhesiveness and organ disposition of the cells has not been obtained. Using positron emission tomography (PET), we have developed a novel technique that enables the non-invasive detection of the real-time tumor cell trafficking. The present study shows the correlation between trafficking of murine large cell lymphoma RAW117 and the adhesion properties of the cells in vitro. Cells accumulated in the liver time-dependently, and accumulation of RAW117-H10, liver metastatic subline cells, was more intense than that of RAW117-P, the parental cells, indicating that the metastatic potential is correlated with the in vivo accumulation of the cells in the target tissue. To examine whether the adhesion properties of the cell membrane determine the cell trafficking, we performed PET analysis after altering the adhesion properties on the cell membrane by means of cellular protein kinase C modulation, since the modulation of this enzyme is known to alter the surface adhesion molecules, i.e., those of the integrin superfamily. The treatment of RAW117-P with 12- O-tetradecanoylphorbol 13-acetate, which caused augmentation of adhesion to hepatic sinusoidal microvessel endothelial cells (HSE) in vitro, enhanced the hepatic accumulation of the cells in vivo. On the contrary, treatment of RAW117-H10 with the protein kinase C inhibitor H-7, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride, which reduced the adhesion activity of the cells to HSE, suppressed their accumulation in the liver, although the suppression was observed only during the first 30 min after administration of the cells. These data suggest that the adhesion properties of metastatic lymphoma cells are critical for the accumulation of these cells in the target tissue.