Conventional Positron Emission Tomography Research Articles

Performance evaluation of a very high resolution small animal PET imager using silicon scatter detectors

A very high resolution positron emission tomography (PET) scanner for small animal imaging based on the idea of inserting a ring of high-granularity solid-state detectors into a conventional PET scanner is under investigation. A particularly interesting configuration of this concept, which takes the form of a degenerate Compton camera, is shown capable of providing sub-millimeter resolution with good sensitivity. We present a Compton PET system and estimate its performance using a proof-of-concept prototype. A prototype single-slice imaging instrument was constructed with two silicon detectors 1 mm thick, each having 512 1.4 mm × 1.4 mm pads arranged in a 32 × 16 array. The silicon detectors were located edgewise on opposite sides and flanked by two non-position sensitive BGO detectors. The scanner performance was measured for its sensitivity, energy, timing, spatial resolution and resolution uniformity. Using the experimental scanner, energy resolution for the silicon detectors is 1%. However, system energy resolution is dominated by the 23% FWHM BGO resolution. Timing resolution for silicon is 82.1 ns FWHM due to time-walk in trigger devices. Using the scattered photons, time resolution between the BGO detectors is 19.4 ns FWHM. Image resolution of 980 µm FWHM at the center of the field-of-view (FOV) is obtained from a 1D profile of a 0.254 mm diameter 18F line source image reconstructed using the conventional 2D filtered back-projection (FBP). The 0.4 mm gap between two line sources is resolved in the image reconstructed with both FBP and the maximum likelihood expectation maximization (ML-EM) algorithm. The experimental instrument demonstrates sub-millimeter resolution. A prototype having sensitivity high enough for initial small animal images can be used for in vivo studies of small animal models of metabolism, molecular mechanism and the development of new radiotracers.

Quantification of β+ activity generated by hard photons by means of PET

Positron emission tomography (PET) as a method for quality assurance in radiotherapy is well investigated in the case of therapy with carbon ion beams and successfully applied at the Heavy Ion Medical Accelerator at Chiba (HIMAC), Japan, and the Gesellschaft für Schwerionenforschung (GSI), Germany. By measuring the β+ activity distribution during the irradiation (in-beam PET), valuable information on the precision of the dose deposition can be obtained. To extend this efficient technique to other radiation treatment modalities may be worthwhile. For example, since positron emitters are generated by high-energy photons with energies above 20 MeV due to (γ, n) reactions (predominantly 11C and 15O in tissue), in-beam PET seems to be feasible for radiation therapy with high-energy photons as also shown in Geant4 simulations. Quantitative results on the activation of tissue-equivalent materials at hard photon beams were obtained by performing off-beam PET experiments. Homogeneous PMMA phantoms as well as inhomogeneous phantoms were irradiated with high-energy bremsstrahlung. After the irradiation the distributions of the generated positron emitters in the phantoms were measured using a conventional PET scanner. Furthermore, the depth–dose distributions were determined by means of optically stimulated luminescence detectors. In the experiments an activity per dose comparable to that produced in a typical patient irradiation with carbon ions could be achieved for 34 MV bremsstrahlung. In addition, a high contrast in the PET images for materials with different density and stoichiometry could be detected. Thus, further research concerning the development of in-beam PET seems to be worthwhile.

Investigation of an internal PET probe for prostate imaging

We present a Monte Carlo simulation study of an application-specific positron emission tomography (PET) imaging device for the prostate that is capable of higher spatial resolution and sensitivity than a conventional PET scanner. The internal detector consists of an array of 1 mm×1 mm×3 mm LSO crystals coupled with avalanche photodiodes. The internal detector works in coincidence with a conventional external PET scanner to record two sets of coincidences: those occurring between the internal detector and the external ring, and conventional PET coincidences occurring between detectors of the external ring. Because of its proximity to the prostate, information from the internal detector supports both high resolution (∼1 mm FWHM) and efficiency while coincidence events recorded solely by the external detector provide complete tomographic data for image reconstruction.

Positron emission tomography with 18F-FDG in osteoarthritic knee

To evaluate osteoarthritis (OA) of the knee using positron emission tomography (PET) with 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) as a tracer. Fifteen patients with medial-type knee OA and three healthy subjects were enrolled in the study. After clinical examination and conventional radiography, (18)F-FDG PET and magnetic resonance imaging (MRI) were performed. (18)F-FDG uptake was quantified as a standardized uptake value (SUV) and the localization of (18)F-FDG uptake was identified using fusion images created with MRI scans. (18)F-FDG generally accumulated in periarticular lesions and was absent in the articular cartilage. SUVs of the whole knee were higher in OA than in controls, and those in the medial condyle were higher than in the lateral condyle in OA. Prominent (18)F-FDG uptake was found in the intercondylar notch in OA and extended along the posterior cruciate ligament (PCL) in some cases. Periosteophytic accumulation was found in one-half of cases with definite osteophytes. Accumulation was also found in subchondral lesions and bone marrow, which corresponded with bone edema diagnosed by MRI. No significant correlation was found between SUV and clinical manifestations. (18)F-FDG uptake was upregulated in OA and generally accumulated in periarticular lesions. Increased uptake was found in the intercondylar notch extending along the PCL, periosteophytic lesions, and bone marrow. These results provide in vivo pathognomonic insights into OA.

Gastric Distension by Ingesting Food Is Useful in the Evaluation of Primary Gastric Cancer by FDG PET

Gastric carcinoma is the second leading cause of cancer-related death worldwide. Detection and surgical resection of gastric cancer in the early stage provides the only hope for improved survival in patients with gastric cancer. Positron emission tomography (PET) with F-18 2-deoxy-2-fluoro-D-glucose (FDG) has been shown to be essential in the evaluation of a variety of malignancies. However, conventional FDG PET has limited value for detecting a primary tumor of the stomach, mostly because of the relatively high levels of physiological uptake by the contracted stomach. We report 3 cases of primary gastric carcinomas detected successfully by FDG PET after the ingestion of food. The PET images of the stomach after ingesting food were compared with the routine fasting-state whole-body PET images for each patient. When the stomach was distended by food, the malignant lesions were more discernible. These cases indicate that gastric distension by ingesting food may be a simple method that can help to detect a primary gastric malignancy by FDG PET.

Invited commentary

The article by de Pas and colleagues [1de Pas TM, de Braud F, Catalano G, et al. Oligometastatic non-small cell lung cancer: a multidisciplinary approach in the position emission tomographic scan era. Ann Thorac Surg 2007;83:231–5.Google Scholar] describes the management of stage IV lung cancer with a solitary metastasis in the positron-emission tomographic scan era. Previous studies have reported that whole-body positron-emission tomography (PET) for lung cancer staging detected occult distal metastases in 6% to 17% of patients for whom conventional clinical methods failed to identify [2Hellwig D. Ukena D. Paulsen F. Bamberg M. Kirsch C.M. Meta-analysis of the efficacy of positron emission tomography with F-18-fluorodeoxyglucose in lung tumors Basis for discussion of the German Consensus Conference on PET in Oncology 2000.Pneumologie. 2001; 55: 367-377Crossref PubMed Scopus (138) Google Scholar, 3Lardinois D. Weder W. Hany T.F. et al.Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography.N Engl J Med. 2003; 348: 2500-2507Crossref PubMed Scopus (1252) Google Scholar]. Indeed the incidence of patients with synchronous solitary metastatic deposits evaluated by conventional work-up and PET is small. For this highly selective subset of 10 of a total of 1,509 patients, the investigators found a potential for long-term survival after a multidisciplinary treatment approach including local complete resection of the primary lung cancer. In this setting, the experience mirrors what thoracic surgeons go through at some point. We are supported by the literature in acknowledging the negative prognosis of patients with stage IV nonsmall cell lung cancer, but an individualized indication for a subset of patients with singular metastatic lesions suggests that surgical resection in a multidisciplinary treatment approach may be beneficial and can achieve prolonged survival. Few investigators have reported patients who have undergone a curative treatment regimen for oligometastatic lung cancer. The rarity of solitary metastatic disease in patients who are candidates for surgical resection of the primary lung cancer makes it unlikely for larger randomized prospective trials to compare different treatment regimens. The absence of prognostic factors that could predict survival benefit makes it impossible to preoperatively identify the subgroups of patients who would benefit from an aggressive treatment regimen. For now it seems reasonable to recommend that if complete resection of the primary lung cancer can be achieved, the solitary hematogenous metastasis should be considered for further localized therapeutic modalities. The role of chemotherapy in a combined treatment protocol remains unclear in this subset of patients [4Downey R.J. Ng K.K. Kris M.G. et al.A phase II trial of chemotherapy and surgery for non-small cell lung cancer patients with a synchronous solitary metastasis.Lung Cancer. 2002; 38: 193-197Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar]. Given the relatively poor results reported with radiation and chemotherapy in adrenal metastases, an aggressive surgical approach may be warranted even as a palliative procedure [5Higashiyama M. Doi O. Kodama K. Yokouchi H. Imaoka S. Koyama H. Surgical treatment of adrenal metastasis following pulmonary resection for lung cancer: comparison of adrenalectomy with palliative therapy.Int Surg. 1994; 79: 124-129PubMed Google Scholar]. The 18-fluorine-fluorodeoxyglucose (18FDG) PET scan is needed in this subset of patients to restrict surgery as a multimodality treatment to those who will potentially benefit from this type of treatment. As the authors conclude, the 18FDG-PET scan is recommended to help screen out patients with nonsmall cell lung cancer who are erroneously diagnosed with single metastatic disease. Oligometastatic Non–Small Cell Lung Cancer: A Multidisciplinary Approach in the Positron Emission Tomographic Scan EraThe Annals of Thoracic SurgeryVol. 83Issue 1PreviewWe have assessed the survival rate of patients with non–small cell lung cancer and synchronous hematogenous solitary metastasis identified with complete staging workup, including total body [18F]fluorodeoxyglucose positron emission tomography scan, and treated with a multidisciplinary approach. Full-Text PDF

FDG-PET in Peripheral T-Cell Lymphoma.

The sensitivity and specificity of fluorine-18 fluoro-deoxy-glucose positron emission tomography (PET) in the evaluation of peripheral T cell lymphomas (PTCL) is not well established. In this abstract, we describe our experience utilizing PET in the diagnostic evaluation of PTCL.A retrospective review of 2768 PET examinations conducted at our institutionbetween the years 1999–2006 produced twenty-six examinations among twenty-two patients with a biopsy proven diagnosis of PTCL. All patients underwent staging of their disease using both conventional diagnostic methods and PET. Their therapeutic status was also taken into consideration when interpreting PET examinations. PTCL were classified by World Health Organization (WHO) criteria and included: PTCL-unclassified (PTCL-U), anaplastic lymphoma kinase positive (+) and negative (−) anaplastic large cell lymphoma, gioimmunoblastic (AITL n=1), and natural killer T-cell nasal type (NK/T n=1). PET results for each patient were compared against a standard of reference, and the sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PET) of PET were calculated.PET had an overall sensitivity of 55% and specificity of 100% in PTCL-U. PET had an overall sensitivity of 83% and specificity of 100% in ALCL. PET had an overall sensitivity of 13% and specificity of 0% in cutaneous PTCL. Among patients with non-cutaneous PTCL-U, the sensitivity and specificity were 83% and 100% respectively. Among patients with non-cutaneous ALCL, the sensitivity and specificity were 100% respectively. Excluding those patients with cutaneous PTCL, PET correlated with clinical outcome in 87% of PTCL-U 100% of ALCL patients. The average maximum standard uptake value (g/mL) of abnormal foci demonstrated greater intensity in patients with ALCL (13.1) than those with PTCL-U (8.87) (Figure 1). PET had excellent correlation with CT, physical examination and clinical follow-up at both nodal and extra-nodal sites, but poor correlation at cutaneous sites (Figure 2).The PPV and NPV of restaging PET in PTCL-U were 75% and 100% respectively. In ALCL, the PPV and NPV of restaging PET were 66% and 100% respectively.PET is useful for staging and restaging patients with nodal and non-cutaneous extra-nodal involvement in PTCL-U and ALCL. It demonstrates a comparatively low sensitivity in cutaneous PTCL. [Display omitted] [Display omitted]

Inter-crystal scatter identification for a depth-sensitive detector using support vector machine for small animal positron emission tomography

In a conventional positron emission tomography (PET) detector, detected events are projected onto a 2D position histogram by an Anger calculation for crystal identification. However, the measured histogram is affected by inter-crystal scatterings (ICS) which occur in the entire detector. Peaks which are projected for each crystal in the histogram are blurred, and this causes ICS mispositioning. A depth-of-interaction (DOI) detector has been developed for the small animal PET scanner jPET-RD. This DOI detector uses 32×32 crystals with four layers and a 256-channel multi-anode flat panel photomultiplier tube (FP-PMT) which was developed by Hamamatsu Photonics K.K. Each crystal element is 1.45×1.45×4.5 mm 3. The FP-PMT has a large detective area (49×49 mm 2) and a small anode pitch (3.04 mm). Therefore, the FP-PMT can extensively trace the behavior of incident γ rays in the crystals including ICS event. We, therefore, propose a novel method for ICS estimation using a statistical pattern recognition algorithm based on a support vector machine (SVM). In this study, we applied the SVM for discriminating photoelectric events from ICS events generated from multiple-anode outputs. The SVM was trained by uniform irradiation events generated from a detector simulator using a Monte Carlo calculation. The success rate for ICS event identification is about 78% for non-training data. The SVM can achieve a true subtraction of ICS events from measured events, and it is also useful for random correction in PET.

Potential Time Benefit in the Assessment of Recurrent Rat Rhabdomyosarcoma Using Positron Emission Tomography (PET) with 18Fluorodeoxyglucose Depends on Therapy-Specific Growth Delay

To correlate the potential time benefit of (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) in terms of early detection of recurrences of subcutaneously growing R1H tumors with therapy-specific parameters of recurrent tumor. Twelve, eleven, and seven recurrences were followed after fractionated radiotherapy, surgery, and chemotherapy for 6 months, respectively, and (18)FDG-PET was performed weekly using a conventional full-ring whole-body PET scanner. By comparing PET results and actual tumor volume, the time benefit of (18)FDG-PET in detection of recurrent tumors of 0.1, 0.2, and 0.5 cm(3) was determined for the different treatment strategies. A significant time benefit of (18)FDG-PET of 26.9 days and 67 days was solely determined for recurrences after radiotherapy of 0.2 cm(3) and 0.5 cm(3), respectively. The potential time benefit showed a strong correlation with growth delay, which was increased after radiotherapy due to a pronounced tumor-bed effect. The potential time benefit of (18)FDG-PET is strongly determined by the growth kinetics of the recurrence. A tumor-bed effect, which is a phenomenon solely seen after radiotherapy, favors early detection by (18)FDG-PET. The experimental data, clinical experience and theoretical consideration all indicate a noticeable benefit of (18)FDG-PET especially after radiotherapeutic treatment.

RF Transformer Coupled Multiplexing Circuits for APD PET Detectors

Avalanche-photodiodes (APDs) as photosensors in positron emission tomography (PET) detectors have been extensively investigated in this field. Compared with conventional photosensors such as the photomultiplier tubes (PMTs), most APDs have advantages of higher quantum efficiency (~70% for APD vs. ~20% for PMT), robust packaging and very low magnetic susceptibility. However, it usually has very low gain (~200 for APD vs. ~10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> for PMT), and a smaller photoactive area (~ 5 mmtimes5 mm for APD vs. 10-52 mm diameter for PMT). The proposal described in this paper was based on a previous APD block detector design, in which each block consists of a 2times2 APD array reading out an 8times8 array of Lutetium Oxyorthosilicate (LSO) crystals. Each crystal is 2 mmtimes2 mmtimes20 mm. Due to the small block size, in order to build an APD PET system with similar axial field-of-view of a conventional PET scanner, substantially more APD detectors would be needed. Consequently, more electronics processing channels would be required. To simplify the detector electronics, we initiate a multiplexing concept based on RF transformers. This approach may reduce the signal-processing channels by a factor of 16 (from 64 channels to four). The circuits would work from both current and voltage sources, as opposed to resistor networks which map signals only from current sources. We built prototype printed-circuit-boards (PCBs) to evaluate different multiplexing schemes. The initial measurements demonstrate that the multiplexing circuits can be implemented in the detector electronics to reduce signal output channels, without increasing signal rise-time and degrading signal-to-noise ratio (SNR). The detector maintains an energy resolution of 19% and timing resolution of about 2 ns (block to single crystal). Moreover, the transformer can function as a single-ended (pseudo-differential) to true-differential converter; this would facilitate retaining signal integrity in transmission through long twisted-pair cables

Medical Imaging

Medical Imaging

PET-Probe: Evaluation of Technical Performance and Clinical Utility of a Handheld High-Energy Gamma Probe in Oncologic Surgery

Positron emission tomography (PET) has become an invaluable part of patient evaluation in surgical oncology. PET is less than optimal for detecting lesions <1 cm, and the intraoperative localization of small PET-positive lesions can be challenging as a result of difficulties in surgical exposure. We undertook this investigation to assess the utility of a handheld high-energy gamma probe (PET-Probe) for intraoperative identification of 18F-deoxyglucose (FDG)-avid tumors. Forty patients underwent a diagnostic whole-body FDG-PET scan for consideration for surgical exploration and resection. Before surgery, all patients received an intravenous injection of 7 to 10 mCi of FDG. At surgery, the PET-Probe was used to determine absolute counts per second at the known tumor site(s) demonstrated by whole-body PET and at adjacent normal tissue (at least 4 cm away from tumor-bearing sites). Tumor-to-background ratios were calculated. Thirty-two patients (80%) underwent PET-Probe-guided surgery with therapeutic intent in a recurrent or metastatic disease setting. Eight patients underwent surgery for diagnostic exploration. Anatomical locations of the PET-identified lesions were neck and supraclavicular (n = 8), axilla (n = 5), groin and deep iliac (n = 4), trunk and extremity soft tissue (n = 3), abdominal and retroperitoneal (n = 19), and lung (n = 2). PET-Probe detected all PET-positive lesions. The PET-Probe was instrumental in localization of lesions in 15 patients that were not immediately apparent by surgical exploration. The PET-Probe identified all lesions demonstrated by PET scanning and, in selected cases, was useful in localizing FDG-avid disease not seen with conventional PET scanning.

Quantitative measurement of oxygen metabolic rate in the rat brain using microPET imaging of briefly inhaled 15O-labelled oxygen gas

The quantitative measurement of cerebral metabolic rate of oxygen (CMRO(2)) for rats using positron emission tomography (PET) has been technically difficult. The present study was performed to provide a technique to measure CMRO(2) for rats using a dedicated animal PET technique. CMRO(2) in the rat brain was quantitatively measured under alpha-chloralose anaesthesia (30 mg . kg(-1) . h(-1), intravenous infusion) using a PET imaging technique. In our experiment, the (15)O-labelled gas tracer (O(15)O) was administered by a bolus insufflation into the lung through a surgically placed cannula in the trachea. The tracer distribution was then dynamically imaged using the microPET. Unlike other conventional PET methods in which a series of arterial blood samples need to be withdrawn for the measurement of an arterial input function, no arterial blood sampling was employed. Instead, the heart was scanned in dynamic mode at the same time of imaging the brain, and the region of interest drawn over the heart was analysed to obtain an arterial input function. The CMRO(2) value (micromol . 100 g(-1) . min(-1)) from 10 rats was 208 +/- 15 (mean +/- SD). Our results suggest that the microPET-based CMRO(2) measurement in the rat brain combined with a non-invasive measurement of arterial input function is promising, especially for many applications involving small animals in which repeated measurements of absolute CMRO(2) need to be performed.

Performance of triple coincidence imaging as an addition to dedicated PET

In this work, we investigate the performance of semiconductor detectors imaging capabilities in three-photon annihilation processes in order to combine this novel imaging modality with conventional positron emission tomography. The spatial resolution is studied as a function of detector positions and selected energy window. This was measured from different experimental arrangements and found to be in the range between 3.3–3.9 cm with a mean of 3.5±0.1 cm. Scatter and random events, coincidence timing resolution and count rate performance are discussed.

18F-2-Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Scanning Affects Surgical Management in Selected Patients With High-Risk, Operable Breast Carcinoma

The role of positron emission tomography (PET) scanning in determining the extent of disease in patients with breast cancer has not been defined. We investigated the utility of (18)F-2-fluoro-2-deoxy-D: -glucose (FDG)-PET scanning compared with conventional imaging with computed tomographic scanning and bone scanning in determining the extent of disease in patients with high-risk, operable breast cancer. This was a prospective study of patients who presented to Memorial Sloan-Kettering Cancer Center for operative treatment of breast cancer. Eighty eligible patients were enrolled and underwent computed tomographic chest, abdomen, pelvis, and bone scans, followed by FDG-PET. Changes in treatment based on scan findings were recorded by the operating surgeons. Imaging findings were verified by biopsy or long-term follow-up. Eight (10%) of 80 patients were found to have metastatic disease that was seen on both conventional imaging and PET. Four additional patients (5%) had additional foci of disease on PET that affected treatment decisions. No patient had findings on conventional imaging alone. Conventional imaging studies resulted in a higher number of findings that generated additional tests and biopsies that ultimately had negative results (17% vs. 5% for PET). There was a statistically significant difference in specificity for PET compared with conventional imaging (P = .01). Conventional imaging and PET were equally sensitive in detecting metastatic disease in patients with high-risk, operable breast cancer, but PET generated fewer false-positive results. FDG-PET scanning should be further studied in this setting and considered in the preoperative evaluation of selected patients with breast cancer.

Fully automatic diagnostic system for early- and late-onset mild Alzheimer’s disease using FDG PET and 3D-SSP

The purpose of this study was to design a fully automatic computer-assisted diagnostic system for early- and late-onset mild Alzheimer's disease (AD). Glucose metabolic images were obtained from mild AD patients and normal controls using positron emission tomography (PET) and( 18)F-fluorodeoxyglucose (FDG). Two groups of 20 mild AD patients with different ages of onset were examined. A fully automatic diagnostic system using the statistical brain mapping method was established from the early-onset (EO) and late-onset (LO) groups, with mean ages of 59.1 and 70.9 years and mean MMSE scores of 23.3 and 22.8, respectively. Aged-matched normal subjects were used as controls. We compared the diagnostic performance of visual inspection of conventional axial FDG PET images by experts and beginners with that of our fully automatic diagnostic system in another 15 EO and 15 LO AD patients (mean age 58.4 and 71.7, mean MMSE 23.6 and 23.1, respectively) and 30 age-matched normal controls. A receiver operating characteristic (ROC) analysis was performed to compare data. The diagnostic performance of the automatic diagnostic system was comparable with that of visual inspection by experts. The area under the ROC curve for the automatic diagnostic system was 0.967 for EO AD patients and 0.878 for LO AD patients. The mean area under the ROC curve for visual inspection by experts was 0.863 and 0.881 for the EO and LO AD patients, respectively. The mean area under the ROC curve for visual inspection by beginners was 0.828 and 0.717, respectively. The fully automatic diagnostic system for EO and LO AD was able to perform at a similar diagnostic level to visual inspection of conventional axial images by experts.

Non-invasive quantification of cerebral blood flow for rats by microPET imaging of 15O labelled water: the application of a cardiac time???activity curve for the tracer arterial input function

In-vivo quantitative cerebral blood flow (CBF) measurement using positron emission tomography (PET) has typically employed invasive arterial blood sampling procedure to determine the arterial input function (AIF). The present study was performed to provide a non-invasive quantitative CBF measurement technique for rats using a dedicated animal PET. CBF was measured in 10 male rats (Fischer 344, 247-290 g) under alpha-chloralose anesthesia (30 mg x kg . h, intravenous infusion) by dynamic PET imaging employing the intravenous bolus injection of H2(15)O. Unlike other conventional PET methods, no arterial blood sampling was employed. Instead, a cardiac time-activity curve (TAC) obtained from the dynamic PET imaging was used to determine the AIF. For the validation of this technique, CBF was also measured by calculating the washout rate of the tracer (H2(15)O) following an intracarotid bolus injection. CBF measurements by two independent methods were done while modulating and maintaining the body temperature at two different levels (32+/-1 and 37+/-1 degrees C by the rectal temperature). Two methods were compared by the linear regression analysis. CBF (ml x 100 g x min) values (mean+/-SD) were 45.2+/-6.05 (intravenous) and 47.4+/-8.64 (intracarotid) at the hypothermic condition (32 degrees C), and 55.1+/-4.88 (intravenous) and 54.4+/-4.60 (intracarotid) at the normothermic condition (37 degrees C). There was a good agreement between the two methods (r=0.70). Our cardiac TAC analysis technique for small animals can be used for the non-invasive quantification of CBF using the PET-based in-vivo imaging technique.

Suppression of random coincidences during in-beam PET measurements at ion beam radiotherapy facilities

In-beam positron emission tomography (PET) is currently the only method for an in-situ monitoring of charged hadron therapy. However, in-beam PET data, measured at beams with a sub-/spl mu/s-microstructure due to the accelerator radio frequency (RF), are highly corrupted by random coincidences arising from prompt /spl gamma/ rays following nuclear reactions as the projectiles penetrate the tissue. Since random-correction techniques from conventional PET cannot be applied, the clinical in-beam PET at the therapy facility at the Gesellschaft fur Schwerionenforschung (GSI), Darmstadt, Germany, merely reconstructs events registered in the pauses (/spl sim/2--4 s) between the beam macropulses (/spl les/2 s). We have successfully tested two methods for suppressing the micropulse-induced random coincidences during beam extraction. Image statistics can be increased by about 90%. Both methods rely on the synchronization of the /spl gamma//spl gamma/ coincidences measured by the positron camera with the time microstructure of the beam, either by using the RF signal from the accelerator or the signal of a thin diamond detector placed in the beam path in front of the target. Energy and triple-coincidence time-correlated spectra first measured during beam extraction, combined with the corresponding tomographic images of the /spl beta//sup +/ activity induced by the beam in a plastic phantom, clearly confirm the feasibility of the proposed random suppression methods. These methods provide the solution for applying in-beam PET at synchrotron and cyclotron radiotherapy facilities with optimal use of the annihilation photon flux.

Noninvasive imaging of transgene expression by use of positron emission tomography in a pig model of myocardial gene transfer.

Radionuclide imaging of reporter gene expression may be useful for noninvasive monitoring of clinical cardiac gene therapy. Experience until now, however, has been limited to small animals. To evaluate feasibility in a clinically applicable setting, pigs were studied by conventional positron emission tomography (PET) 2 days after regional intramyocardial injection of control adenovirus or adenovirus carrying herpesviral thymidine kinase reporter gene (HSV1-tk). Myocardial blood flow was quantified by use of [13N]ammonia. Subsequently, kinetics of the reporter substrate [124I]-2'-fluoro-2'-deoxy-5-iodo-1-beta-d-arabino-furanosyluracil (FIAU) were assessed over a period of 2 hours. Areas infected with adenovirus expressing HSV1-tk showed significantly elevated FIAU retention during the first 30 minutes after injection. At later times, washout was observed, and retention was not different from that in areas infected with control virus or remote myocardium. Early in vivo FIAU uptake correlated with ex vivo images, autoradiography, and immunohistochemistry for reporter gene product after euthanasia. After intramyocardial injection of both adenoviruses, myocardial blood flow was mildly elevated compared with that in remote areas, consistent with histological signs of regional inflammation. In vivo quantification of regional myocardial transgene expression is feasible with clinical PET methodology, the radioiodinated reporter probe FIAU, and the HSV1-tk reporter gene. Radioactivity efflux after specific initial uptake was not observed previously in tumor studies, suggesting that tissue-specific differences in nucleoside metabolism influence reporter probe kinetics. By coregistering reporter gene expression with additional biological parameters such as myocardial blood flow, PET allows for noninvasive characterization of the success of cardiac gene transfer along with its functional correlates.

Diagnosis in medullary thyroid cancer with [18F]FDG-PET and improvement using a combined PET/CT scanner.

Today, positron emission tomography (PET) investigation using fluorodeoxyglucose (FDG) is the most sensitive and specific single modality established for localizing metastases of medullary thyroid cancer (MTC). Even at calcitonin serum levels below 20 pg/ml, tumour localization may be successful in individual cases. However, especially in such early tumour stages, the morphological correlation using PET is unsatisfactory. With the newly available fixed combination of PET and computed tomography (PET/CT), this drawback can be overcome as PET/CT allows a point-by-point correlation of pathological function with morphological structure. Conventional PET alone yielded an approx 80 % sensitivity and specificity in MTC: a result that will be surpassed by the combined PET/CT scanner.