A red tide of Alexandrium fundyense in the Gulf of Maine.

In early July 2009, an unusually high concentration of the toxic dinoflagellate Alexandrium fundyense occurred in the western Gulf of Maine, causing surface waters to appear reddish brown to the human eye. The discolored water appeared to be the southern terminus of a large-scale event that caused shellfish toxicity along the entire coast of Maine to the Canadian border. Rapid-response shipboard sampling efforts together with satellite data suggest the water discoloration in the western Gulf of Maine was a highly ephemeral feature of less than two weeks in duration. Flow cytometric analysis of surface samples from the red water indicated the population was undergoing sexual reproduction. Cyst fluxes downstream of the discolored water were the highest ever measured in the Gulf of Maine, and a large deposit of new cysts was observed that fall. Although the mechanisms causing this event remain unknown, its timing coincided with an anomalous period of downwelling-favorable winds that could have played a role in aggregating upward-swimming cells. Regardless of the underlying causes, this event highlights the importance of short-term episodic phenomena on regional population dynamics of A. fundyense.

Georges Bank: a leaky incubator of Alexandrium fundyense blooms.

A series of oceanographic surveys on Georges Bank document variability of populations of the toxic dinoflagellate Alexandrium fundyense on time scales ranging from synoptic to seasonal to interannual. Blooms of A. fundyense on Georges Bank can reach concentrations on the order of 104 cells l-1, and are generally bank-wide in extent. Georges Bank populations of A. fundyense appear to be quasi-independent of those in the adjacent coastal Gulf of Maine, insofar as they occupy a hydrographic niche that is colder and saltier than their coastal counterparts. In contrast to coastal populations that rely on abundant resting cysts for bloom initiation, very few cysts are present in the sediments on Georges Bank. Bloom dynamics must therefore be largely controlled by the balance between growth and mortality processes, which are at present largely unknown for this population. Based on correlations between cell abundance and nutrient distributions, ammonium appears to be an important source of nitrogen for A. fundyense blooms on Georges Bank.

Suppression of the 2010 Alexandrium fundyense bloom by changes in physical, biological, and chemical properties of the Gulf of Maine.

For the period 2005-2009, the abundance of resting cysts in bottom sediments from the preceding fall was a first-order predictor of the overall severity of spring-summer blooms of Alexandrium fundyense in the western Gulf of Maine and southern New England. Cyst abundance off mid-coast Maine was significantly higher in fall 2009 than it was preceding a major regional bloom in 2005. A seasonal ensemble forecast was computed using a range of forcing conditions for the period 2004-2009, suggesting that a large bloom was likely in the western Gulf of Maine in 2010. This did not materialize, perhaps because environmental conditions in spring-summer 2010 were not favorable for growth of A.fundyense. Water mass anomalies indicate a regional-scale change in circulation with direct influence on A. fundyense's niche. Specifically, near-surface waters were warmer, fresher, more stratified, and had lower nutrients than during the period of observations used to construct the ensemble forecast. Moreover, a weaker-than-normal coastal current lessened A. fundyense transport into the western Gulf of Maine and Massachusetts Bay. Satellite ocean color observations indicate the 2010 spring phytoplankton bloom was more intense than usual. Early-season nutrient depletion may have caused a temporal mismatch with A. fundyense's endogenous clock that regulates the timing of cyst germination. These findings highlight the difficulties of ecological forecasting in a changing oceanographic environment, and underscore the need for a sustained observational network to drive such forecasts.

Physical principles and technology of clinical PET imaging.

Molecular imaging with positron-emitting radionuclides is playing an increasingly important role in the diagnosis and staging of malignant disease and in monitoring response to therapy. To meet this challenge, significant improvements in the performance of the imaging technology have been achieved in recent years. Such developments are subject to the constraints imposed by the physics of positron emission tomography (PET) and the main objectives in designing or improving PET scanners are to achieve high spatial resolution and sensitivity while maximising the true coincidence count rate relative to contributions from noise processes. Noise contributions in PET include not only statistical effects associated with photon counting but also background processes such as scatter and random coincidences. The recent developments of new, faster scintillators and electronics for PET detectors, as well as statistically-based algorithms that reconstruct fully three-dimensional (3D) PET images in minutes, have dramatically reduced clinical imaging times while improving image quality. A recent advance, the combination of functional imaging and computed tomography (CT) in the PET/CT scanner has further reduced the study duration by eliminating the lengthy PET transmission scan and providing accurate anatomical localisation of functional abnormalities. PET imaging technology has now improved to where a combined anatomical and functional clinical study can be completed in less than 10 minutes--although taking advantage of such high throughput potential will challenge patient management in diagnostic imaging departments. This paper reviews the physical principles underlying PET and summarises the recent developments in PET scanner technology, from the introduction of new PET detectors to the development of the combined PET/CT scanner.

Dual-modality PET/CT tomography for clinical oncology.

Diagnosis and follow-up in clinical oncology are traditionally based on computed tomography (CT). In recent years, however, functional imaging using positron emission tomography (PET) has been recognized as an important imaging modality and adjunct to CT that provides complementary metabolic information in many oncology applications. To overcome the challenges of aligning independently acquired PET and CT image sets several ad hoc concepts of integrating PET and CT imaging in a single device have been proposed. This article comments on the development of the first combined dual-modality PET/CT prototype at the University of Pittsburgh, and illustrates commercial advances to dual-modality PET/CT tomography. The current PET/CT designs from the major manufacturers comprise a commercial CT scanner in tandem with a commercial PET scanner. While the level of physical integration is actually less than that of the original prototype it is fair to assume that current PET/CT models may serve as intermediate solutions towards near-future design concepts that aim at greatly reduced costs of the dual-modality tomographs and offer a greater level of physical integration. The goal of the next generation of PET/CT systems is to design and build a device specifically for imaging the function and anatomy of cancer in the most informative and effective way without necessarily conceptualizing it as combined PET and CT scanners. Such a concept of a diagnostic imaging device relates more to a disease management approach rather than the usual division into medical specialities such as radiology and nuclear medicine.

Positron emission tomography/computed tomography imaging for the detection of recurrent ovarian and fallopian tube carcinoma: a retrospective review.

PURPOSE: Imaging modalities to evaluate ovarian/fallopian tube cancer patients for recurrence are limited. Positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound lack the sensitivity to consistently detect recurrence or measurable disease in these patients. A new technique combines PET and CT (PET/CT) images to identify increased metabolic activity and to locate that signal with improved anatomic specificity. The objective of this study is to compare PET/CT, CT, and histologic findings in patients with recurrent ovarian/fallopian tube cancers. METHODS: Retrospective chart review of eight patients with primary ovarian (n = 6) or fallopian tube (n = 2) cancer was performed. All eight patients underwent initial cytoreductive surgery. Five patients initially received chemotherapy, one received radioactive phosphorus ((32)P), one received tamoxifen, and one received no therapy. Seven of eight patients had a suspected recurrence based on clinical examination, elevated CA-125 level, and/or abnormal CT findings; one patient requested a PET/CT. Histologic findings from surgery were correlated with PET/CT and CT findings. RESULTS: All eight patients had positive histology, and of these, seven patients had a negative CT and five patients had lesions that were correctly identified by PET/CT. CONCLUSIONS: Five of the eight (62%) patients had recurrent disease based on correlative histology with a positive PET/CT and a negative CT. These preliminary findings suggest that combined PET/CT may be an effective means of identifying patients with recurrent ovarian/fallopian tube cancer. Such patients could potentially proceed to salvage treatment and avoid the morbidity and expense of surgical assessment. Pilot studies comparing CT, PET, PET/CT, and histologic findings are underway.

The role of positron emission tomography in evaluating mediastinal lymph node metastases in non-small-cell lung cancer.

Positron emission tomography (PET) is a modality that differentiates malignant from benign processes based upon metabolism rather than anatomy. A number of studies have confirmed improved accuracy of PET over computed tomography (CT), but until a few recent studies, most had failed to include satisfactory histologic confirmation. The objective of this study was to compare PET and CT to histologic staging of the mediastinum in patients with non-small-cell lung cancer (NSCLC). Histologic examination of mediastinal lymph nodes (MLNs) was performed on 40 patients with NSCLC at mediastinoscopy and/or at surgical resection. PET scans were interpreted by one of two nuclear medicine physicians, blinded to histology, using CT scans for anatomic localization. CT scans were independently evaluated for mediastinal lymphadenopathy. The overall accuracy, sensitivity, and specificity of PET were 78% (31 of 40), 67% (four of six), and 79% (27 of 34), respectively. The overall accuracy, sensitivity, and specificity of CT were 68% (27 of 40), 50% (three of six), and 71% (24 of 34), respectively. PET was superior to CT at correctly identifying mediastinal nodal metastases; however, both modalities were inferior to the gold standard of surgical staging. PET is more accurate than CT in staging the mediastinum of patients with NSCLC. PET failed to identify lymph node metastasis in 33% of patients with histologically proven MLN involvement, and false positives were present in 15%. At present, mediastinoscopy should remain the standard of care for preoperative mediastinal staging for NSCLC.

Whole-body FDG positron emission tomographic imaging for staging esophageal cancer comparison with computed tomography.

PURPOSE: The aim of the authors in this study was to critically evaluate the role of whole-body positron emission tomographic (PET) imaging with fluorine-18 fluorodeoxyglucose (FDG) in staging esophageal cancer, and further to compare this method with conventional imaging with computed tomography (CT). MATERIALS AND METHODS: The authors performed independent, blinded retrospective evaluations of FDG PET images obtained in 47 patients referred for the initial staging of esophageal cancer before minimally invasive surgical staging. Twenty PET studies from patients with nonesophageal thoracic cancers were randomly selected for inclusion in the PET readings. In a subset of 37 of 47 cases, the PET findings were compared with independent readings of CT studies acquired within the same 6-week interval. The utility of the imaging findings was evaluated using a high-sensitivity interpretation (i.e., assigning equivocal findings as positive) and a low-sensitivity interpretation (i.e., assigning equivocal findings as negative). RESULTS: PET was less sensitive (41% in high-sensitivity mode, 35% in low-sensitivity mode) than CT (63% to 87%) for diagnosing tumor involvement in locoregional lymph nodes, which was identified by surgical assessment in 72% of patients. Notable, however, was the greater specificity of PET-determined nodal sites (to approximately 90%) compared with CT (14% to 43%). In detecting histologically proved distant metastases (n = 10), PET performed considerably better when applied in the high-sensitivity mode, with a sensitivity rate of approximately 70% and a specificity rate of more than 90% in the total group and in the subset of patients with correlative CT data. In the low-sensitivity mode, CT identified only two of seven metastatic sites, whereas the high-sensitivity mode resulted in an unacceptably high rate of false-positive readings (positive predictive value, 29%). PET correctly identified one additional site of metastasis that was not detected by CT. CONCLUSIONS: The relatively low sensitivity of PET for identifying locoregional lesions precludes its replacement of conventional CT staging. However, the primary advantage of PET imaging is its superior specificity for tumor detection and improved diagnostic value for distant metastatic sites, features that may substantially affect patient management decisions. In conclusion, PET imaging is useful in the initial staging of esophageal cancer and provides additional and complementary information to that obtained by CT imaging.

Image analysis in patients with cancer studied with a combined PET and CT scanner.

PURPOSE: To compare combined whole-body PET and CT images of different cancers with PET images alone. MATERIALS AND METHODS: Thirty-two patients with known or possible cancers were examined using a combined positron emission tomographic (PET) and computed tomographic (CT) scanner. All data were acquired using this same combined scanner. After an injection of F-18 fluorodeoxyglucose (FDG), noncontrast helical CT imaging of the neck, chest, abdomen, or pelvis was performed. The spiral CT was followed by a PET scan covering the same axial extent as the CT. RESULTS: Coregistered PET-CT images identified and localized 55 lesions. In 10 patients (31%), areas with variable amounts of normal physiologic FDG uptake were distinguished from potential uptake of FDG in a nearby neoplastic lesion. Improved localization was achieved in 9 patients (for a total of 13 lesions, or 24%). CONCLUSION: Combined PET-CT images appear more effective than PET images alone to localize precisely neoplastic lesions and to distinguish normal variants from juxtaposed neoplastic lesions.

A combined PET/CT scanner for clinical oncology.

UNLABELLED: The availability of accurately aligned, whole-body anatomical (CT) and functional (PET) images could have a significant impact on diagnosing and staging malignant disease and on identifying and localizing metastases. Computer algorithms to align CT and PET images acquired on different scanners are generally successful for the brain, whereas image alignment in other regions of the body is more problematic. METHODS: A combined PET/CT tomograph with the unique capability of acquiring accurately aligned functional and anatomical images for any part of the human body has been designed and built. The PET/CT scanner was developed as a combination of a Siemens Somatom AR.SP spiral CT and a partial-ring, rotating ECAT ART PET scanner. All components are mounted on a common rotational support within a single gantry. The PET and CT components can be operated either separately, or in combined mode. In combined mode, the CT images are used to correct the PET data for scatter and attenuation. Fully quantitative whole-body images are obtained for an axial extent of 100 cm in an imaging time of less than 1 h. When operated in PET mode alone, transmission scans are acquired with dual 137Cs sources. RESULTS: The scanner is fully operational and the combined device has been operated successfully in a clinical environment. Over 110 patients have been imaged, covering a range of different cancers, including lung, esophageal, head and neck, melanoma, lymphoma, pancreas, and renal cell. The aligned PET and CT images are used both for diagnosing and staging disease and for evaluating response to therapy. We report the first performance measurements from the scanner and present some illustrative clinical studies acquired in cancer patients. CONCLUSION: A combined PET and CT scanner is a practical and effective approach to acquiring co-registered anatomical and functional images in a single scanning session.

Combined PET/CT Imaging in Oncology. Impact on Patient Management.

Purpose: In this work, we describe five oncology patients whose clinical management were uniquely benefited by a novel scanner that acquires positron emission tomography (PET) and x-ray computed tomography (CT) in the same imaging session.Procedures: Co-registered 2-[F(18)]-fluoro-2-deoxy-D-glucose (FDG)-PET and CT images were acquired using a combined PET/CT scanner. Pathology and clinical follow-up data were used to confirm PET/CT scan results.Results: The combined PET/CT scanner demonstrated the ability to distinguish malignant lesions from normal physiologic FDG uptake in the striated muscles of the head and neck as well as excretory and bowel activity in the abdomen and pelvis. Additionally, the technology positively affected patient management through localization for surgical and radiation therapy planning as well as assessment of tumor response.Conclusion: Our experience indicates that simultaneous acquisition of co-registered PET and CT images enabled physicians to more precisely discriminate between physiologic and malignant FDG uptake and more accurately localize lesions, improving the value of diagnostic PET in oncologic applications.

Superphysiologic FDG Uptake in the Non-Paralyzed Vocal Cord. Resolution of a False-Positive PET Result with Combined PET-CT Imaging.

The application of positron emission tomography imaging with 18F-fluorodeoxyglucose (FDG) to the extracranial head and neck has been proven to be effective in the detection and staging of malignancy. The FDG uptake of normal laryngeal tissue is symmetric and low, while benign lesions typically have only slight increases in FDG uptake. We report a case of asymmetric, superphysiologic FDG uptake in the contralateral vocal cord of a patient with a unilateral vocal cord paralysis secondary to sacrifice of the recurrent laryngeal nerve during pneumonectomy for lung cancer. The FDG uptake of the non-paralyzed vocal cord was increased multiple-fold, placing it well within the range of malignancy. Use of unique, combined PET-CT imaging localized the high FDG uptake to the non-paralyzed vocal cord, and laryngoscopy confirmed no evidence of malignancy in the vocal cord. This case demonstrates that a benign cause of false-positive FDG-PET imaging may be encountered during evaluation of the extracranial head and neck for malignancy. We aim to alert the reader to this potential pitfall in the interpretation of FDG-PET imaging, which can be resolved with the use of combined PET-CT imaging and clinical correlation.

Evaluation of distant metastases in esophageal cancer: 100 consecutive positron emission tomography scans.

BACKGROUND: Pilot studies suggest positron emission tomography (PET) scanning may be superior to conventional imaging in staging esophageal cancer, especially in the detection of radiographically occult distant metastases. This report summarizes our experience with PET in staging esophageal cancer. METHODS: One hundred consecutive PET scans in 91 patients with esophageal cancer referred for surgery were prospectively collected (1995 to 1998) and compared with computerized tomography (CT) and bone scan. PET images were acquired after injection of 18F-fluorodeoxyglucose and evaluated for abnormal uptake. Minimally invasive surgical staging (MIS) and/or clinical correlation were used to confirm or refute imaging results. RESULTS: MIS or clinical correlation confirmed 70 distant metastases in 39 cases. PET detected 51 metastases in 27 of 39 cases (69% sensitivity, 93.4% specificity, 84% accuracy) compared with CT, which detected 26 metastases in 18 of 39 cases (46.1% sensitivity, 73.8% specificity, 63% accuracy) (p < 0.01). CONCLUSIONS: PET was more accurate than CT in detecting distant metastases, but was only 69% sensitive compared with minimally invasive staging.

Attenuation correction for a combined 3D PET/CT scanner.

In this work we demonstrate the proof of principle of CT-based attenuation correction of 3D positron emission tomography (PET) data by using scans of bone and soft tissue equivalent phantoms and scans of humans. This method of attenuation correction is intended for use in a single scanner that combines volume-imaging (3D) PET with x-ray computed tomography (CT) for the purpose of providing accurately registered anatomical localization of structures seen in the PET image. The goal of this work is to determine if we can perform attenuation correction of the PET emission data using accurately aligned CT attenuation information. We discuss possible methods of calculating the PET attenuation map at 511 keV based on CT transmission information acquired from 40 keV through 140 keV. Data were acquired on separate CT and PET scanners and were aligned using standard image registration procedures. Results are presented on three of the attenuation calculation methods: segmentation, scaling, and our proposed hybrid segmentation/scaling method. The results are compared with those using the standard 3D PET attenuation correction method as a gold standard. We demonstrate the efficacy of our proposed hybrid method for converting the CT attenuation map from an effective CT photon energy of 70 keV to the PET photon energy of 511 keV. We conclude that using CT information is a feasible way to obtain attenuation correction factors for 3D PET.

FDG imaging of spinal cord primitive neuroectodermal tumor.

PET with 18F-fluoro-2-deoxy-glucose (FDG) is well established as an effective imaging modality for evaluating suspected brain tumor recurrence. Use of FDG PET imaging for spinal cord neoplasms has not yet been studied, in large part due to limitations of spatial resolution. One report of FDG PET imaging of brain involvement with primitive neuroectodermal tumor (PNET) demonstrated mild hypometabolism relative to cortical gray matter. We demonstrate with FDG PET imaging the appearance of recurrent intramedullary PNET affecting the cervical spinal cord.

Fluorine-18-fluorodeoxyglucose uptake in pneumonia.

Whole-body PET imaging with 18F-fluorodeoxyglucose (FDG) has been shown to be effective in distinguishing benign and malignant pulmonary disease. Mild elevations in FDG uptake with standardized uptake values (SUVs) less than 2.5 have been reported in benign lesions, including pneumonia. We report a case of presumed bacterial pneumonia with markedly elevated FDG uptake in a patient with a concomitant squamous cell carcinoma in the contralateral lung. SUV's were similar for both lesions (4.9 and 5.4). This case demonstrates an inflammatory etiology for false-positive FDG PET imaging in the evaluation of focal pulmonary abnormalities.

Minimally invasive surgical biopsy confirms PET findings in esophageal cancer.

This report describes our initial experience using positron emission tomography (PET) scanning in esophageal cancer patients. In two patients PET identified distant metastatic disease missed by conventional staging. Laparoscopic biopsy provided histological confirmation of metastases. In the third patient, locoregional lymph nodes were identified by PET and confirmed by surgical staging. In this preliminary report, PET appears to be a promising new noninvasive modality for staging patients with esophageal cancer.

Role of positron emission tomography in staging esophageal cancer.

BACKGROUND: Conventional noninvasive staging of esophageal cancer is inaccurate. This study investigated the role of positron emission tomography (PET) in staging esophageal cancer. METHODS: Patients with potentially resectable esophageal cancer were included. A whole-body PET scan was acquired after injection of 18F-fluorodeoxyglucose and was evaluated for areas of increased focal uptake. Accuracy was determined by comparing PET with surgical staging. RESULTS: Potentially resectable esophageal cancer was identified in 35 patients. Positron emission tomography detected nine sites of distant metastases missed by conventional scanning, but one false-negative PET scan occurred in a patient with a 2-mm liver lesion. There were 11 false-negative PET scans for small, intracapsular local-regional nodal metastases (mean diameter 5.2 mm; range 2 to 10 mm). For distant metastases, the sensitivity was 88%, the specificity was 93%, and the accuracy was 91%. For local-regional nodal metastases, the sensitivity was 45%, the specificity was 100%, and the accuracy was 48%. CONCLUSIONS: Positron emission tomography improved our ability to detect distant metastases missed by conventional noninvasive staging of esophageal cancer. Small local-regional nodal metastases are not identified by current PET technology. Early use of PET in the staging of patients with esophageal cancer could facilitate treatment planning and identifying unsuspected distant metastases in up to 20% of patients with a negative metastatic survey by conventional staging.

A multicompartment model of vitamin B6 metabolism.

The shape of the labelling curve for urinary pyridoxic acid following a single dose of labelled pyridoxine can be most easily described by a two compartment model. However, the usefulness of such a model is limited because the two pools have no physiological identity; the model does not describe the many metabolic interconversions associated with vitamin B6 metabolism; and the predictions of the total size of the vitamin B6 pool are not consistent with data from direct measurements. Therefore, we have been using the Simulation, Analysis, and Modelling program (SAAM) developed at the National Cancer Institute to develop an improved model. Since the SAAM 29 program is limited to 25 pools, only a few of the many tissue vitamin B6 pools could be included. Muscle and liver were chosen because they contain 80 to 90% of the vitamin B6 in the body. Plasma and erythrocytes were selected because of their importance in transport. This review traces the development of the model to its current stage and shows comparisons between the predictions of the model and a variety of data from the literature. At this point the emphasis has been on describing metabolism in rats because the most detailed kinetic data available were obtained from rats. The predictions of the current model do not match all available observations. However, the results are sufficiently encouraging to warrant continued development.

Dopa oxidase activity in human hair bulbs measured by high-performance liquid chromatography.

A method for measuring the dopa oxidase (DO) activity of human hair bulb tyrosinase has been developed and the results of this method have been compared with the tyrosine hydroxylase (TH) activity of hair bulb tyrosinase for brown-, black-, blond-, and red-haired subjects. The method takes advantage of the rapid trapping of dopaquinone by cysteine with the subsequent formation of cysteinyldopas which can be measured by high-performance liquid chromatography. 5-S-Cysteinyldopa (5SCD) and 2-S-cysteinyldopa (2SCD) were detected in the reaction products. Formation of 5SCD correlated with the TH activity over the full range of hair colors and enzyme activity, while 2SCD appeared to be formed nonenzymatically. The absolute amount of 2SCD was constant for each individual but did not correlate with hair color or TH activity. The formation of 5SCD was linear for 60 min while most of the 2SCD was formed within seconds and did not change with time. White hair bulbs which demonstrated no TH activity formed 2SCD, but not 5SCD. We conclude that tyrosinase activity can be quantitated in human hair bulbs by this method, and that TH and DO are coordinate functions of tyrosinase over a broad range of hair color and enzyme activity.