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.

Nutrients and water masses in the Gulf of Maine - Georges Bank region: Variability and importance to blooms of the toxic dinoflagellate Alexandrium fundyense.

We report here the results of ten oceanographic survey cruises carried out in the Gulf of Maine - Georges Bank region of the Northwest Atlantic during the late spring to summer period in 2007, 2008 and 2010, for which we examine and characterize relationships among dissolved inorganic nutrient fields, water mass dynamics and cell densities of the toxic dinoflagellate Alexandrium fundyense. Nutrients are supplied to continental shelf waters of the Gulf of Maine - Georges Bank region by inflows of deep offshore water masses; once in the Gulf they are transported with the residual circulation and mix with surface waters, both in the Gulf and on the Bank. Those fluxes of offshore water masses and their nutrient loads are the major source of nutrients for phytoplankton production in the region, including annual blooms of A. fundyense in the Gulf and on Georges Bank. This much is already known. We suggest here that the locations and magnitude of A. fundyense blooms are controlled in part by variable nutrient fluxes to the interior Gulf of Maine from offshore, and, those interior Gulf of Maine waters are, in turn, the main nutrient source to Georges Bank, which are brought onto the Bank by tidal pumping on the Northern Flank. We present evidence that nitrate is the initial form of nitrogenous nutrient for A. fundyense blooms, but it is quickly depleted to limiting concentrations of less than 0.5 µM, at which time continued growth and maintenance of the population is likely fueled by recycled ammonium. We also show that phosphate may be the limiting nutrient over much of Georges Bank in summer, allowing recycled ammonium concentrations to increase. Our temperature-salinity analyses reveal spatial and temporal (seasonal and interannual) variability in the relative proportions of two deep source waters that enter the Gulf of Maine at depth through the Northeast Channel: Warm Slope Water (WSW) and Labrador Slope Water (LSW). Those two source waters are known to vary in their nutrient loads, with nitrate concentrations about 50% higher in WSW than LSW, for example, and as such the proportions of these two water masses to one another are important determinants of the overall nutrient loads in the interior Gulf. In addition to these deep slope water fluxes, we show evidence here of episodic fluxes of relatively fresh and low-nutrient shelf waters from the Nova Scotian Shelf, which enter the Gulf in pulses at depths between the surface and approximately 150 m, displacing deep slope waters, and consequently they significantly dilute the Gulf's interior waters, reducing nutrient concentrations and, in turn, affect the magnitude of A. fundyense blooms.

Physical and clinical performance of the mCT time-of-flight PET/CT scanner.

Time-of-flight (TOF) measurement capability promises to improve PET image quality. We characterized the physical and clinical PET performance of the first Biograph mCT TOF PET/CT scanner (Siemens Medical Solutions USA, Inc.) in comparison with its predecessor, the Biograph TruePoint TrueV. In particular, we defined the improvements with TOF. The physical performance was evaluated according to the National Electrical Manufacturers Association (NEMA) NU 2-2007 standard with additional measurements to specifically address the TOF capability. Patient data were analyzed to obtain the clinical performance of the scanner. As expected for the same size crystal detectors, a similar spatial resolution was measured on the mCT as on the TruePoint TrueV. The mCT demonstrated modestly higher sensitivity (increase by 19.7 ± 2.8%) and peak noise equivalent count rate (NECR) (increase by 15.5 ± 5.7%) with similar scatter fractions. The energy, time and spatial resolutions for a varying single count rate of up to 55 Mcps resulted in 11.5 ± 0.2% (FWHM), 527.5 ± 4.9 ps (FWHM) and 4.1 ± 0.0 mm (FWHM), respectively. With the addition of TOF, the mCT also produced substantially higher image contrast recovery and signal-to-noise ratios in a clinically-relevant phantom geometry. The benefits of TOF were clearly demonstrated in representative patient images.

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.

Multimodality imaging of structure and function.

Historically, medical devices to image either anatomical structure or functional processes have developed along somewhat independent paths. The recognition that combining images from different modalities can nevertheless offer significant diagnostic advantages gave rise to sophisticated software techniques to coregister structure and function. Recently, alternatives to retrospective software-based fusion have become available through instrumentation that combines two imaging modalities within a single device, an approach that has since been termed hardware fusion. As a result, following their recent introduction into the clinic, combined PET/CT and SPECT/CT devices are now playing an increasingly important role in the diagnosis and staging of human disease. Recently, although limited to the brain, the first clinical MR scanner with a PET insert, a technically-challenging design, has been undergoing evaluation. This review will follow the development of multimodality instrumentation for clinical use from conception to present-day technology and assess the status and future potential for such devices.

Fast fully 3-D image reconstruction in PET using planograms.

We present a method of performing fast and accurate three-dimensional (3-D) backprojection using only Fourier transform operations for line-integral data acquired by planar detector arrays in positron emission tomography. This approach is a 3-D extension of the two-dimensional (2-D) linogram technique of Edholm. By using a special choice of parameters to index a line of response (LOR) for a pair of planar detectors, rather than the conventional parameters used to index a LOR for a circular tomograph, all the LORs passing through a point in the field of view (FOV) lie on a 2-D plane in the four-dimensional (4-D) data space. Thus, backprojection of all the LORs passing through a point in the FOV corresponds to integration of a 2-D plane through the 4-D "planogram." The key step is that the integration along a set of parallel 2-D planes through the planogram, that is, backprojection of a plane of points, can be replaced by a 2-D section through the origin of the 4-D Fourier transform of the data. Backprojection can be performed as a sequence of Fourier transform operations, for faster implementation. In addition, we derive the central-section theorem for planogram format data, and also derive a reconstruction filter for both backprojection-filtering and filtered-backprojection reconstruction algorithms. With software-based Fourier transform calculations we provide preliminary comparisons of planogram backprojection to standard 3-D backprojection and demonstrate a reduction in computation time by a factor of approximately 15.

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.

Cerebral responses to noxious thermal stimulation in chronic low back pain patients and normal controls.

Changes in regional cerebral blood flow (rCBF) have previously been demonstrated in a number of cortical and subcortical regions, including the cerebellum, midbrain, thalamus, lentiform nucleus, and the insula, prefrontal, anterior cingulate, and parietal cortices, in response to experimental noxious stimuli. Increased anterior cingulate responses in patients with chronic regional pain and depression to noxious stimulation distant from the site of clinical pain have been observed. We suggested that this may represent a generalized hyperattentional response to noxious stimuli and may apply to other types of chronic regional pain. Here these techniques are extended to a group of patients with nonspecific chronic low back pain. Thirty-two subjects, 16 chronic low back pain patients and 16 controls, were studied using positron emission tomography. Thermal stimuli, corresponding to the experience of hot, mild, and moderate pain, were delivered to the back of the subject's right hand using a thermal probe. Each subject had 12 measurements of rCBF, 4 for each stimulus. Correlation of rCBF with subjective pain experience revealed similar responses across groups in the cerebellum, midbrain (including the PAG), thalamus, insula, lentiform nucleus, and midcingulate (area 24') cortex. These regions represented the majority of activations for this study and those recorded by other imaging studies of pain. Although some small differences were observed between the groups these were not considered sufficient to suggest abnormal nociceptive processing in patients with nonspecific low back pain.

Combining anatomy and function: the path to true image fusion.

Modern imaging technologies visualize different aspects of disease in a non-invasive way. Considerable progress has been made in the fusion of images from different imaging modalities using software approaches. One goal of fusion software is to align anatomical and functional images and allow improved spatial localization of abnormalities. The resulting correlation of the anatomical and functional images may clarify the nature of the abnormality and help diagnose or stage the underlying disease. Whereas successful image fusion software has been developed for the brain, only limited success has been achieved for image alignment in other parts of the body. The development and current status of alternative approaches are presented. Dual-modality imaging is described with devices where two modalities are combined and mounted in a single gantry. The use of existing scanner technology ensures that no compromises are made in the clinical efficacy of either the anatomical or functional imaging modality. A combined positron emission tomography (PET) and computed tomography (CT) scanner has been developed and is undergoing clinical evaluation. Combining PET with MR is technologically more challenging because of the strong magnetic fields restricting the use of certain electronic components. An overview of the current status and future prospects of dual-modality imaging devices is presented.

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.

Planned ictal FDG PET imaging for localization of extratemporal epileptic foci.

PURPOSE: This work demonstrates the feasibility of planned ictal positron emission tomography (PET) with [18F]fluoro-2-deoxy-glucose (FDG) for localization of epileptic activity in patients with frequent partial seizures of extratemporal origin. METHODS: Ictal PET imaging was performed in four patients (two men and two women, ages 28-61) with continuous or very frequent (every 3-15 min) partial seizures. All patients had abnormalities apparent on magnetic resonance (MR) or computed tomographic (CT) imaging, two with extensive brain lesions that precluded precise localization of the seizure focus with interictal PET or single-photon emission tomography (SPECT) imaging. RESULTS: Ictal PET imaging demonstrated a restricted area of focal hypermetabolism concordant with surface electroencephalographic (EEG) recording in all cases. The PET images were registered to MR imaging data for further anatomic localization of hypermetabolic regions in three cases. The ictal PET data were used to guide neurosurgical intervention in one case. CONCLUSIONS: We conclude that planned ictal PET imaging may be a useful and potentially superior approach to ictal SPECT for identifying the epileptic focus in a selected group of patients with continuous or frequent simple partial seizures.

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.