Validation of low-dose lung cancer PET-CT protocol and PET image improvement using machine learning.

PURPOSE: To conduct a simplified lesion-detection task of a low-dose (LD) PET-CT protocol for frequent lung screening using 30% of the effective PETCT dose and to investigate the feasibility of increasing clinical value of low-statistics scans using machine learning. METHODS: We acquired 33 SD PET images, of which 13 had actual LD (ALD) PET, and simulated LD (SLD) PET images at seven different count levels from the SD PET scans. We employed image quality transfer (IQT), a machine learning algorithm that performs patch-regression to map parameters from low-quality to high-quality images. At each count level, patches extracted from 23 pairs of SD/SLD PET images were used to train three IQT models - global linear, single tree, and random forest regressions with cubic patch sizes of 3 and 5 voxels. The models were then used to estimate SD images from LD images at each count level for 10 unseen subjects. Lesion-detection task was carried out on matched lesion-present and lesion-absent images. RESULTS: LD PET-CT protocol yielded lesion detectability with sensitivity of 0.98 and specificity of 1. Random forest algorithm with cubic patch size of 5 allowed further 11.7% reduction in the effective PETCT dose without compromising lesion detectability, but underestimated SUV by 30%. CONCLUSION: LD PET-CT protocol was validated for lesion detection using ALD PET scans. Substantial image quality improvement or additional dose reduction while preserving clinical values can be achieved using machine learning methods though SUV quantification may be biased and adjustment of our research protocol is required for clinical use.

Pseudo-nitzschia bloom dynamics in the Gulf of Maine: 2012-2016.

The toxic diatom genus Pseudo-nitzschia is a growing presence in the Gulf of Maine (GOM), where regionally unprecedented levels of domoic acid (DA) in 2016 led to the first Amnesic Shellfish Poisoning closures in the region. However, factors driving GOM Pseudo-nitzschia dynamics, DA concentrations, and the 2016 event are unclear. Water samples were collected at the surface and at depth in offshore transects in summer 2012, 2014, and 2015, and fall 2016, and a weekly time series of surface water samples was collected in 2013. Temperature and salinity data were obtained from NERACOOS buoys and measurements during sample collection. Samples were processed for particulate DA (pDA), dissolved nutrients (nitrate, ammonium, silicic acid, and phosphate), and cellular abundance. Species composition was estimated via Automated Ribosomal Intergenic Spacer Analysis (ARISA), a semi-quantitative DNA finger-printing tool. Pseudo-nitzschia biogeography was consistent in the years 2012, 2014, and 2015, with greater Pseudo-nitzschia cell abundance and P. plurisecta dominance in low-salinity inshore samples, and lower Pseudo-nitzschia cell abundance and P. delicatissima and P. seriata dominance in high-salinity offshore samples. During the 2016 event, pDA concentrations were an order of magnitude higher than in previous years, and inshore-offshore contrasts in biogeography were weak, with P. australis present in every sample. Patterns in temporal and spatial variability confirm that pDA increases with the abundance and the cellular DA of Pseudo-nitzschia species, but was not correlated with any one environmental factor. The greater pDA in 2016 was caused by P. australis - the observation of which is unprecedented in the region - and may have been exacerbated by low residual silicic acid. The novel presence of P. australis may be due to local growth conditions, the introduction of a population with an anomalous water mass, or both factors. A definitive cause of the 2016 bloom remains unknown, and continued DA monitoring in the GOM is warranted.

Quality Improvement Initiatives to Assess and Improve PET/CT Injection Infiltration Rates at Multiple Centers.

PET/CT radiotracer infiltration is not uncommon and is often outside the imaging field of view. Infiltration can negatively affect image quality, image quantification, and patient management. Until recently, there has not been a simple way to routinely practice PET radiopharmaceutical administration quality control and quality assurance. Our objectives were to quantify infiltration rates, determine associative factors for infiltration, and assess whether rates could be reduced at multiple centers and then sustained. Methods: A "design, measure, analyze, improve, and control" quality improvement methodology requiring novel technology was used to try to improve PET/CT injection quality. Teams were educated on the importance of quality injections. Baseline infiltration rates were measured, center-specific associative factors were analyzed, team meetings were held, improvement plans were established and executed, and rates remeasured. To ensure that injection-quality gains were retained, real-time feedback and ongoing monitoring were used. Sustainability was assessed. Results: Seven centers and 56 technologists provided data on 5,541 injections. The centers' aggregated baseline infiltration rate was 6.2% (range, 2%-16%). On the basis of their specific associative factors, 4 centers developed improvement plans and reduced their aggregated infiltration rate from 8.9% to 4.6% (P < 0.0001). Ongoing injection monitoring showed sustainability. Significant variation was found in center- and technologist-level infiltration rates (P < 0.0001 and P = 0.0020, respectively). Conclusion: A quality improvement approach with new technology can help centers measure infiltration rates, determine associative factors, implement interventions, and improve and sustain injection quality. Because PET/CT images help guide patient management, the monitoring and improvement of radiotracer injection quality are important.

Sub-clinical abnormalities detected by PET/MRI in household tuberculosis contacts.

BACKGROUND: The understanding of early events following TB exposure is limited by traditional tests that rely on detection of an immune response to infection, which is delayed, or on imaging tests with low sensitivity for early disease. We investigated for evidence of lung abnormalities in heavily exposed TB contacts using PET/MRI. METHODS: 30 household contacts of 20 index patients underwent clinical assessment, IGRA testing, chest x-ray and PET/MRI scan using 18-F-FDG. MRI images were examined by a radiology/nuclear medicine dual-qualified physician using a standardised report form, while PET/MRI images were examined independently by another radiology/nuclear medicine dual-qualified physician using a similar form. Standardised uptake value (SUV) was quantified for each abnormal lesion. RESULTS: IGRA was positive in 40%. PET/MRI scan was abnormal in 30%, predominantly FDG uptake in hilar or mediastinal lymph nodes and lung apices. We did not identify any relationship between PET/MRI findings and degree of exposure or IGRA status. CONCLUSION: PET-based imaging may provide important insights into the natural history following exposure to TB that may not be available from traditional tests of TB immune response or imaging. The clinical significance of the abnormalities is uncertain and merits further investigation in longitudinal studies.

Usefulness of Topically Applied Sensors to Assess the Quality of 18F-FDG Injections and Validation Against Dynamic Positron Emission Tomography (PET) Images.

Background: Infiltrations of 18F-fluorodeoxyglucose (FDG) injections affect positron emission tomography/computed tomography (PET/CT) image quality and quantification. A device using scintillation sensors (Lucerno Dynamics, Cary, NC) provides dynamic measurements acquired during FDG uptake to identify and characterize radioactivity near the injection site prior to patient imaging. Our aim was to compare sensor measurements against dynamic PET image acquisition, our proposed reference in assessing injection quality during the uptake period. Methods: Subjects undergoing routine FDG PET/CT imaging were eligible for this Institutional Review Board approved prospective study. After providing informed consent, subjects had sensors topically placed on their arms. FDG was injected into subjects' veins directly on the PET imaging table. Dynamic images of the injection site were acquired during 45 min of the uptake period. These dynamic image acquisitions and subjects' routine standard static images were evaluated by nuclear medicine physicians for abnormal FDG accumulation near the injection site. Sensor measurements were interpreted independently by Lucerno staff. Dynamic image acquisition interpretation results were compared to the sensor measurement interpretations and to static image interpretations. Results: Twenty-four subjects were consented and enrolled. Data from 21 subjects were gathered. During dynamic image acquisition review, physicians interpreted 4 subjects with no FDG accumulation at the injection site, whereas 17 showed evidence of accumulation. In 10 of the 17 cases that showed FDG accumulation, the FDG presence at the injection site resolved completely during uptake corresponding to venous stasis, the temporary sequestration of blood from circulation. Static image interpretation agreed with dynamic images interpretation in 11/21 (52%) subjects. Sensor measurement interpretations agreed with the dynamic images interpretations in 18/21 (86%) subjects. Conclusions: Sensor measurements can be an effective way to identify and characterize infiltrations and venous stasis. Comparable to an infiltration, venous stasis may produce spurious and clinically meaningful measurement bias and possibly even scan misinterpretation. Since the quality and quantification of PET/CT studies are of clinical importance, sensor measurements acquired during the FDG uptake may prove to be a useful quality control measure to reduce infiltration rates and potentially improve patient care. Registration: Clinicaltrials.gov, Identifier: NCT03041090.

Development of a Dedicated Rebinner with Rigid Motion Correction for the mMR PET/MR Scanner, and Validation in a Large Cohort of 11C-PIB Scans.

Head motion occurring during brain PET studies leads to image blurring and to bias in measured local quantities. The objective of this work was to implement a correction method for PET data acquired with the mMR synchronous PET/MR scanner. Methods: A list-mode-based motion-correction approach has been designed. The developed rebinner chronologically reads the recorded events from the Siemens list-mode file, applies the estimated geometric transformations, and frames the detected counts into sinograms. The rigid-body motion parameters were estimated from an initial dynamic reconstruction of the PET data. We then optimized the correction for 11C-Pittsburgh compound B (11C-PIB) scans using simulated and actual data with well-controlled motion. Results: An efficient list-mode-based motion correction approach has been implemented, fully optimized, and validated using simulated and actual PET data. The average spatial resolution loss induced by inaccuracies in motion parameter estimates and by the rebinning process was estimated to correspond to a 1-mm increase in full width at half maximum with motion parameters estimated directly from the PET data with a temporal frequency of 20 s. The results show that the rebinner can be safely applied to the 11C-PIB scans, allowing almost complete removal of motion-induced artifacts. The application of the correction method to a large cohort of 11C-PIB scans led to the following observations: first, that more than 21% of the scans were affected by motion greater than 10 mm (39% for subjects with Mini-Mental State Examination scores below 20), and second, that the correction led to quantitative changes in Alzheimer-specific cortical regions of up to 30%. Conclusion: The rebinner allows accurate motion correction at a cost of minimal resolution reduction. Application of the correction to a large cohort of 11C-PIB scans confirmed the necessity of systematically correcting for motion to obtain quantitative results.

Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT-positive humans confirmed by positron emission tomography scan.

Background: Capsinoids are reported to increase energy expenditure (EE) via brown adipose tissue (BAT) stimulation. However, imaging of BAT activation by capsinoids remains limited. Because BAT activation is a potential therapeutic strategy for obesity and related metabolic disorders, we sought to prove that capsinoid-induced BAT activation can be visualized by 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Objective: We compared capsinoids and cold exposure on BAT activation and whole-body EE. Design: Twenty healthy participants (8 men, 12 women) with a mean age of 26 y (range: 21-35 y) and a body mass index (kg/m2) of 21.7 (range: 18.5-26.0) underwent 18F-FDG PET and whole-body calorimetry after ingestion of 12 mg capsinoids or ≤2 h of cold exposure (∼14.5°C) in a crossover design. Mean standardized uptake values (SUVs) of the region of interest and BAT volumes were calculated. Blood metabolites were measured before and 2 h after each treatment. Results: All of the participants showed negligible 18F-FDG uptake post-capsinoid ingestion. Upon cold exposure, 12 participants showed avid 18F-FDG uptake into supraclavicular and lateral neck adipose tissues (BAT-positive group), whereas the remaining 8 participants (BAT-negative group) showed undetectable uptake. Capsinoids and cold exposure increased EE, although cold induced a 2-fold increase in whole-body EE and higher fat oxidation, insulin sensitivity, and HDL cholesterol compared with capsinoids. Conclusions: Capsinoids only increased EE in BAT-positive participants, which suggests that BAT mediates EE evoked by capsinoids. This implies that capsinoids stimulate BAT to a lesser degree than cold exposure as evidenced by 18F-FDG uptake below the presently accepted SUV thresholds defining BAT activation. This trial was registered at www.clinicaltrials.gov as NCT02964442.

Hybrid PET/CT and PET/MRI imaging of vulnerable coronary plaque and myocardial scar tissue in acute myocardial infarction.

BACKGROUND: Following an acute coronary syndrome, combined CT and PET with 18F-NaF can identify coronary atherosclerotic plaques that have ruptured or eroded. However, the processes behind 18F-NaF uptake in vulnerable plaques remain unclear. METHODS AND RESULTS: Ten patients with STEMI were scanned after 18F-NaF injection, for 75 minutes in a Siemens PET/MR scanner using delayed enhancement (LGE). They were then scanned in a Siemens PET/CT scanner for 10 minutes. Tissue-to-background ratio (TBR) was compared between the culprit lesion in the IRA and remote non-culprit lesions in an effort to independently validate prior studies. Additionally, we performed a proof-of-principle study comparing TBR in scar tissue and remote myocardium using LGE images and PET/MR or PET/CT data. From the 33 coronary lesions detected on PET/CT, TBRs for culprit lesions were higher than for non-culprit lesions (TBR = 2.11 ± 0.45 vs 1.46 ± 0.48; P < 0.001). Interestingly, the TBR measured on the PET/CT was higher for infarcted myocardium than for remote myocardium (TBR = 0.81 ± 0.10 vs 0.71 ± 0.05; P = 0.003). These results were confirmed using the PET/MR data (TBR = 0.81 ± 0.10 for scar, TBR = 0.71 ± 0.06 for healthy myocardium, P = 0.03). CONCLUSIONS: We confirmed the potential of 18F-NaF PET/CT imaging to detect vulnerable coronary lesions. Moreover, we demonstrated proof-of-principle that 18F-NaF concurrently detects myocardial scar tissue.

A comparison of 18F-FDG PET/MR with PET/CT in pulmonary tuberculosis.

PURPOSE: PET/computed tomography (CT) has been shown to detect lesions in patients with pulmonary tuberculosis (PTB) and may be useful for assessing PTB disease in clinical research studies. However, radiation dose is of concern for clinical research in individuals with an underlying curable disease. This study aimed to determine whether PET/MR is equivalent to PET/CT in PTB. MATERIALS AND METHODS: Ten patients with microbiologically confirmed PTB were recruited. Patients received 129.0±4.1 MBq of fluorine-18-fluorodeoxyglucose. Five of the 10 patients underwent a PET/MR scan, followed by PET/CT. The remaining five were first imaged on the PET/CT, followed by the PET/MRI. PET acquisition began at 66.7±14.4 min (mean±SD) after injection when performing PET/MR first (PET/CT: 117.2±5.6 min) and 92.4±7.6 min when patients were imaged on PET/MR second (PET/CT: 61.1±3.9 min). PET data were reconstructed iteratively with Ordinary-Poisson Ordered-Subset Expectation-Maximization and reconstruction parameters were matched across the two scanners. A visual lesion detection task and a standardized uptake value (SUV) analysis were carried out. The CT Hounsfield unit values of PTB lesions were also compared with MR-based attenuation correction mu-map tissue classes. RESULTS: A total of 108 PTB lesions were detected on PET/MR and 112 on PET/CT. SUV analysis was carried out on 50 of these lesions that were observed with both modalities. Mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax) were significantly lower on PET/MR (SUVmean: 2.6±1.4; SUVmax: 4.3±2.5) than PET/CT (SUVmean: 3.5±1.5; SUVmax: 5.3±2.4). CONCLUSION: PET/MR visual performance was shown to be comparable to PET/CT in terms of the number of PTB lesions detected. SUVs were significantly lower on PET/MR. Dixon-based attenuation correction underestimates the linear attenuation coefficient of PTB lesions, resulting in lower SUVs compared with PET/CT. However, the use of PET/MR to measure the response of lung lesions to assess response to treatment in research studies is unlikely to be affected by these differences in quantification.

Quantitative 18F-fluorocholine positron emission tomography for prostate cancer: correlation between kinetic parameters and Gleason scoring.

BACKGROUND: The use of radiolabeled choline as a positron emission tomography (PET) agent for imaging primary tumors in the prostate has been evaluated extensively over the past two decades. There are, however, conflicting reports of its sensitivity and the relationship between choline PET imaging and disease staging is not fully understood. Moreover, relatively few studies have investigated the correlation between tracer uptake and histological tumor grade. This work quantified 18F-fluorocholine in tumor and healthy prostate tissue using pharmacokinetic modeling and stratified uptake parameters by histology grade. Additionally, the effect of scan time on the estimation of the kinetic exchange rate constants was evaluated, and the tracer influx parameters from full compartmental analysis were compared to uptake values quantified by Patlak and standardized uptake value (SUV) analyses. 18F-fluorocholine was administered as a 222 MBq bolus injection to ten patients with biopsy-confirmed prostate tumors, and dynamic PET data were acquired for 60 min. Image-derived arterial input functions were scaled by discrete blood samples, and a 2-tissue, 4-parameter model accounting for blood volume (2T4k+Vb) was used to perform fully quantitative compartmental modeling on tumor, healthy prostate, and muscle tissue. Subsequently, all patients underwent radical prostatectomy, and histological analyses were performed on the prostate specimens; kinetic parameters for tumors were stratified by Gleason score. Correlations were investigated between compartmental K 1 and K i parameters and SUV and Patlak slope; the effect of scan time on parameter bias was also evaluated. RESULTS: Choline activity curves in seven tumors, eight healthy prostate regions, and nine muscle regions were analyzed. Net tracer influx was generally higher in tumor relative to healthy prostate, with the values in the highest grade tumors markedly higher than those in lower grade tumors. Influx terms from Patlak and full compartmental modeling showed good correlation within individual tissue groups. Kinetic parameters calculated from the entire 60-min scan data were accurately reproduced from the first 30 min of acquired data (R 2 ≈ 0.9). CONCLUSIONS: Strong correlations were observed between K i and Patlak slope in tumor tissue, and K 1 and SUV were also correlated but to a lesser degree. Reliable estimates of all kinetic parameters can be achieved from the first 30 min of dynamic 18F-choline data. Although SUV, K 1, K i, and Patlak slope were found to be poor differentiators of low-grade tumor compared to healthy prostate tissue, they are strong indicators of aggressive disease.

Quantitative Accuracy and Lesion Detectability of Low-Dose 18F-FDG PET for Lung Cancer Screening.

Lung cancer remains responsible for more deaths worldwide than any other cancer, but recently there has been a significant shift in the clinical paradigm regarding the initial management of subjects at high risk for this disease. Low-dose CT has demonstrated significant improvements over planar x-ray screening for patient prognoses and is now performed in the United States. Specificity of this modality, however, is poor, and the additional information from PET has the potential to improve its accuracy. Routine screening requires consideration of the effective dose delivered to the patient, and this work investigates image quality of PET for low-dose conditions, in the context of lung lesion detectability. Reduced radiotracer doses were simulated by randomly discarding counts from clinical lung cancer scans acquired in list-mode. Bias and reproducibility of lesion activity values were relatively stable even at low total counts of around 5 million trues. Additionally, numeric observer models were developed and trained with the results of 2 physicians and 3 postdoctoral researchers with PET experience in a detection task; detection sensitivity of the observers was well correlated with lesion signal-to-noise ratio. The models were used prospectively to survey detectability of lung cancer lesions, and the findings suggested a lower limit around 10 million true counts for maximizing performance. Under the acquisition parameters used in this study, this translates to an effective patient dose of less than 0.4 mSv, potentially allowing a complete low-dose PET/CT lung screening scan to be obtained under 1 mSv.

Towards real-time topical detection and characterization of FDG dose infiltration prior to PET imaging.

PURPOSE: To dynamically detect and characterize 18F-fluorodeoxyglucose (FDG) dose infiltrations and evaluate their effects on positron emission tomography (PET) standardized uptake values (SUV) at the injection site and in control tissue. METHODS: Investigational gamma scintillation sensors were topically applied to patients with locally advanced breast cancer scheduled to undergo limited whole-body FDG-PET as part of an ongoing clinical study. Relative to the affected breast, sensors were placed on the contralateral injection arm and ipsilateral control arm during the resting uptake phase prior to each patient's PET scan. Time-activity curves (TACs) from the sensors were integrated at varying intervals (0-10, 0-20, 0-30, 0-40, and 30-40 min) post-FDG and the resulting areas under the curve (AUCs) were compared to SUVs obtained from PET. RESULTS: In cases of infiltration, observed in three sensor recordings (30 %), the injection arm TAC shape varied depending on the extent and severity of infiltration. In two of these cases, TAC characteristics suggested the infiltration was partially resolving prior to image acquisition, although it was still apparent on subsequent PET. Areas under the TAC 0-10 and 0-20 min post-FDG were significantly different in infiltrated versus non-infiltrated cases (Mann-Whitney, p < 0.05). When normalized to control, all TAC integration intervals from the injection arm were significantly correlated with SUVpeak and SUVmax measured over the infiltration site (Spearman ρ ≥ 0.77, p < 0.05). Receiver operating characteristic (ROC) analyses, testing the ability of the first 10 min of post-FDG sensor data to predict infiltration visibility on the ensuing PET, yielded an area under the ROC curve of 0.92. CONCLUSIONS: Topical sensors applied near the injection site provide dynamic information from the time of FDG administration through the uptake period and may be useful in detecting infiltrations regardless of PET image field of view. This dynamic information may also complement the static PET image to better characterize the true extent of infiltrations.

Beyond 18F-FDG: Characterization of PET/CT and PET/MR Scanners for a Comprehensive Set of Positron Emitters of Growing Application--18F, 11C, 89Zr, 124I, 68Ga, and 90Y.

UNLABELLED: This study aimed to investigate image quality for a comprehensive set of isotopes ((18)F, (11)C, (89)Zr, (124)I, (68)Ga, and (90)Y) on 2 clinical scanners: a PET/CT scanner and a PET/MR scanner. METHODS: Image quality and spatial resolution were tested according to NU 2-2007 of the National Electrical Manufacturers Association. An image-quality phantom was used to measure contrast recovery, residual bias in a cold area, and background variability. Reconstruction methods available on the 2 scanners were compared, including point-spread-function correction for both scanners and time of flight for the PET/CT scanner. Spatial resolution was measured using point sources and filtered backprojection reconstruction. RESULTS: With the exception of (90)Y, small differences were seen in the hot-sphere contrast recovery of the different isotopes. Cold-sphere contrast recovery was similar across isotopes for all reconstructions, with an improvement seen with time of flight on the PET/CT scanner. The lower-statistic (90)Y scans yielded substantially lower contrast recovery than the other isotopes. When isotopes were compared, there was no difference in measured spatial resolution except for PET/MR axial spatial resolution, which was significantly higher for (124)I and (68)Ga. CONCLUSION: Overall, both scanners produced good images with (18)F, (11)C, (89)Zr, (124)I, (68)Ga, and (90)Y.

Initial assessment of image quality for low-dose PET: evaluation of lesion detectability.

In the context of investigating the potential of low-dose PET imaging for screening applications, we developed methods to assess small lesion detectability as a function of the number of counts in the scan. We present here our methods and preliminary validation using tuberculosis cases. FDG-PET data from seventeen patients presenting diffuse hyper-metabolic lung lesions were selected for the study, to include a wide range of lesion sizes and contrasts. Reduced doses were simulated by randomly discarding events in the PET list mode, and ten realizations at each simulated dose were generated and reconstructed. The data were grouped into 9 categories determined by the number of included true events, from >40 M to <250 k counts. The images reconstructed from the original full statistical set were used to identify lung lesions, and each was, at every simulated dose, quantified by 6 parameters: lesion metabolic volume, lesion-to-background contrast, mean lesion tracer uptake, standard deviation of activity measurements (across realizations), lesion signal-to-noise ratio (SNR), and Hotelling observer SNR. Additionally, a lesion-detection task including 550 images was presented to several experienced image readers for qualitative assessment. Human observer performances were ranked using receiver operating characteristic analysis. The observer results were correlated with the lesion image measurements and used to train mathematical observer models. Absolute sensitivities and specificities of the human observers, as well as the area under the ROC curve, showed clustering and performance similarities among images produced from 5 million or greater counts. The results presented here are from a clinically realistic but highly constrained experiment, and more work is needed to validate these findings with a larger patient population.

MRI-guided brain PET image filtering and partial volume correction.

Positron emission tomography (PET) image quantification is a challenging problem due to limited spatial resolution of acquired data and the resulting partial volume effects (PVE), which depend on the size of the structure studied in relation to the spatial resolution and which may lead to over or underestimation of the true tissue tracer concentration. In addition, it is usually necessary to perform image smoothing either during image reconstruction or afterwards to achieve a reasonable signal-to-noise ratio. Typically, an isotropic Gaussian filtering (GF) is used for this purpose. However, the noise suppression is at the cost of deteriorating spatial resolution. As hybrid imaging devices such as PET/MRI have become available, the complementary information derived from high definition morphologic images could be used to improve the quality of PET images. In this study, first of all, we propose an MRI-guided PET filtering method by adapting a recently proposed local linear model and then incorporate PVE into the model to get a new partial volume correction (PVC) method without parcellation of MRI. In addition, both the new filtering and PVC are voxel-wise non-iterative methods. The performance of the proposed methods were investigated with simulated dynamic FDG brain dataset and (18)F-FDG brain data of a cervical cancer patient acquired with a simultaneous hybrid PET/MR scanner. The initial simulation results demonstrated that MRI-guided PET image filtering can produce less noisy images than traditional GF and bias and coefficient of variation can be further reduced by MRI-guided PET PVC. Moreover, structures can be much better delineated in MRI-guided PET PVC for real brain data.

Water Masses and Nutrient Sources to the Gulf of Maine.

The Gulf of Maine, a semi-enclosed basin on the continental shelf of the northwest Atlantic Ocean, is fed by surface and deep water flows from outside the Gulf: Scotian Shelf Water from the Nova Scotian shelf that enters the Gulf at the surface, and Slope Water that enters at depth and along the bottom through the Northeast Channel. There are two types of Slope Water, Labrador Slope Water (LSW) and Warm Slope Water (WSW); it is these deep water masses that are the major source of dissolved inorganic nutrients to the Gulf. It has been known for some time that the volume inflow of Slope Waters of either type that enters the Gulf of Maine is variable, that it co-varies with the magnitude of inflowing Scotian Shelf Water, and that periods of greater inflows of Scotian Shelf Water have become more frequent in recent years, accompanied by reduced Slope Water inflows. We present here analyses of a ten-year record of data collected by moored sensors in Jordan Basin, in the interior Gulf of Maine, and in the Northeast Channel, along with recent and historical hydrographic and nutrient data, that help reveal the nature of Scotian Shelf Water and Slope Water inflows. Proportional inflows of nutrient-rich Slope Waters and nutrient-poor Scotian Shelf Waters alternate episodically with one another on time scales of months to several years, creating a variable nutrient field upon which the biological productivities of the Gulf of Maine and Georges Bank depend. Unlike decades past, the inflows of Slope Waters of either type do not appear to be correlated with the North Atlantic Oscillation, which had been shown earlier to influence the relative proportions of the two Slope Waters, WSW and LSW, that enter the Gulf. We suggest that of greater importance in recent years are more frequent, episodic influxes of colder, fresher, less dense, and low-nutrient Scotian Shelf Water into the Gulf of Maine, and concomitant reductions in the inflow of deep, nutrient-rich Slope Waters. We also discuss evidence of modified Gulf Stream ring water that penetrated to Jordan Basin in summer of 2013.

Negative contrast Cerenkov luminescence imaging of blood vessels in a tumor mouse model using [68Ga]gallium chloride.

BACKGROUND: Cerenkov luminescence imaging (CLI) is an emerging imaging technique where visible light emitted from injected beta-emitting radionuclides is detected with an optical imaging device. CLI research has mostly been focused on positive contrast imaging for ascertaining the distribution of the radiotracer in a way similar to other nuclear medicine techniques. Rather than using the conventional technique of measuring radiotracer distribution, we present a new approach of negative contrast imaging, where blood vessel attenuation of Cerenkov light emitted by [68Ga]GaCl3 is used to image vasculature. METHODS: BALB/c nude mice were injected subcutaneously in the right flank with HT-1080 fibrosarcoma cells 14 to 21 days prior to imaging. On the imaging day, [68Ga]GaCl3 was injected and the mice were imaged from 45 to 90 min after injection using an IVIS Spectrum in vivo imaging system. The mice were imaged one at a time, and manual focus was used to bring the skin into focus. The smallest view with pixel size around 83 µm was used to achieve a sufficiently high image resolution for blood vessel imaging. RESULTS: The blood vessels in the tumor were clearly visible, attenuating 7% to 18% of the light. Non-tumor side blood vessels had significantly reduced attenuation of 2% to 4%. The difference between the attenuation of light of tumor vessels (10% ± 4%) and the non-tumor vessels (3% ± 1%) was significant. Moreover, a necrotic core confirmed by histology was clearly visible in one of the tumors with a 21% reduction in radiance. CONCLUSIONS: The negative contrast CLI technique is capable of imaging vasculature using [68Ga]GaCl3. Since blood vessels smaller than 50 µm in diameter could be imaged, CLI is able to image structures that conventional nuclear medicine techniques cannot. Thus, the negative contrast imaging technique shows the feasibility of using CLI to perform angiography on superficial blood vessels, demonstrating an advantage over conventional nuclear medicine techniques.