IMRT QA result prediction via MLC transmission decomposition.

BACKGROUND: Quality assurance measurement of IMRT/VMAT treatment plans is resource intensive, and other more efficient methods to achieve the same confidence are desirable. PURPOSE: We aimed to analyze treatment plans in the context of the treatment planning systems that created them, in order to predict which ones will fail a standard quality assurance measurement. To do so, we sought to create a tool external to the treatment planning system that could analyze a set of MLC positions and provide information that could be used to calculate various evaluation metrics. METHODS: The tool was created in Python to read in DICOM plan files and determine the beam fluence fraction incident on each of seven different zones, each classified based on the RayStation MLC model. The fractions, termed grid point fractions, were validated by analyzing simple test plans. The average grid point fractions, over all control points for 46 plans were then computed. These values were then compared with gamma analysis pass percentages and median dose differences to determine if any significant correlations existed. RESULTS: Significant correlation was found between the grid point fraction metrics and median dose differences, but not with gamma analysis pass percentages. Correlations were positive or negative, suggesting differing model parameter value sensitivities, as well as potential insight into the treatment planning system dose model. CONCLUSIONS: By decomposing MLC control points into different transmission zones, it is possible to create a metric that predicts whether the analyzed plan will pass a quality assurance measurement from a dose calculation accuracy standpoint. The tool and metrics developed in this work have potential applications in comparing clinical beam models or identifying their weak points. Implementing the tool within a treatment planning system would also provide more potential plan optimization parameters.

Static MLC transmission simulation using two-dimensional ray tracing.

PURPOSE: We investigated the hypothesis that the transmission function of rounded end linearly traveling multileaf collimators (MLCs) is constant with position. This assumption is made by some MLC models used in clinical treatment planning systems (TPSs) and in the Varian MLC calibration convention. If not constant, this would have implications for treatment plan QA results. METHODS: A two-dimensional ray-tracing tool to generate transmission curves as a function of leaf position was created and validated. The curves for clinically available leaf tip positions (-20 to 20 cm) were analyzed to determine the location of the beam edge (half-attenuation X-ray [XR]) location, the beam edge broadening (BEB, 80%-20% width), as well as the leaf tip zone width. More generalized scenarios were then simulated to elucidate trends as a function of leaf tip radius. RESULTS: In the analysis of the Varian high-definition MLC, two regions were identified: a quasi-static inner region centered about central axis (CAX), and an outer one, in which large deviations were observed. A phenomenon was identified where the half-attenuation ray position, relative to that of the tip or tangential ray, increases dramatically at definitive points from CAX. Similar behavior is seen for BEB. An analysis shows that as the leaf radius parameter value is made smaller, the size of the quasi-static region is greater (and vice versa). CONCLUSION: The MLC transmission curve properties determined by this study have implications both for MLC position calibrations and modeling within TPSs. Two-dimensional ray tracing can be utilized to identify where simple behaviors hold, and where they deviate. These results can help clinical physicists engage with vendors to improve MLC models, subsequent fluence calculations, and hence dose calculation accuracy.

Voxel-Level Dosimetry for Combined Iodine 131 Radiopharmaceutical Therapy and External Beam Radiation Therapy Treatment Paradigms for Head and Neck Cancer.

PURPOSE: Targeted radiopharmaceutical therapy (RPT) in combination with external beam radiation therapy (EBRT) shows promise as a method to increase tumor control and mitigate potential high-grade toxicities associated with re-treatment for patients with recurrent head and neck cancer. This work establishes a patient-specific dosimetry framework that combines Monte Carlo-based dosimetry from the 2 radiation modalities at the voxel level using deformable image registration (DIR) and radiobiological constructs for patients enrolled in a phase 1 clinical trial combining EBRT and RPT. METHODS AND MATERIALS: Serial single-photon emission computed tomography (SPECT)/computed tomography (CT) patient scans were performed at approximately 24, 48, 72, and 168 hours postinjection of 577.2 MBq/m2 (15.6 mCi/m2) CLR 131, an iodine 131-containing RPT agent. Using RayStation, clinical EBRT treatment plans were created with a treatment planning CT (TPCT). SPECT/CT images were deformably registered to the TPCT using the Elastix DIR module in 3D Slicer software and assessed by measuring mean activity concentrations and absorbed doses. Monte Carlo EBRT dosimetry was computed using EGSnrc. RPT dosimetry was conducted using RAPID, a GEANT4-based RPT dosimetry platform. Radiobiological metrics (biologically effective dose and equivalent dose in 2-Gy fractions) were used to combine the 2 radiation modalities. RESULTS: The DIR method provided good agreement for the activity concentrations and calculated absorbed dose in the tumor volumes for the SPECT/CT and TPCT images, with a maximum mean absorbed dose difference of -11.2%. Based on the RPT absorbed dose calculations, 2 to 4 EBRT fractions were removed from patient EBRT treatments. For the combined treatment, the absorbed dose to target volumes ranged from 57.14 to 75.02 Gy. When partial volume corrections were included, the mean equivalent dose in 2-Gy fractions to the planning target volume from EBRT + RPT differed -3.11% to 1.40% compared with EBRT alone. CONCLUSIONS: This work demonstrates the clinical feasibility of performing combined EBRT + RPT dosimetry on TPCT scans. Dosimetry guides treatment decisions for EBRT, and this work provides a bridge for the same paradigm to be implemented within the rapidly emerging clinical RPT space.

Creation of waterproof, TLD probes for dose measurements to validate image-based radiopharmaceutical therapy dosimetry workflow.

Voxel-level dosimetry based on nuclear medicine images offers patient-specific personalization of radiopharmaceutical therapy (RPT) treatments. Clinical evidence is emerging demonstrating improvements in treatment precision in patients when voxel-level dosimetry is used compared to MIRD. Voxel-level dosimetry requires absolute quantification of activity concentrations in the patient, but images from SPECT/CT scanners are not quantitative and require calibration using nuclear medicine phantoms. While phantom studies can validate a scanner's ability to recover activity concentrations, these studies provide only a surrogate for the true metric of interest: absorbed doses. Measurements using thermoluminescent dosimeters (TLDs) are a versatile and accurate method of measuring absorbed dose. In this work, a TLD probe was manufactured that can fit into currently available nuclear medicine phantoms for the measurement of absorbed dose of RPT agents. Next, 748 MBq of I-131 was administered to a 16 ml hollow source sphere placed in a 6.4 L Jaszczak phantom in addition to six TLD probes, each holding 4 TLD-100 1 × 1 × 1 mm TLD-100 (LiF:Mg,Ti) microcubes. The phantom then underwent a SPECT/CT scan in accordance with a standard SPECT/CT imaging protocol for I-131. The SPECT/CT images were then input into a Monte Carlo based RPT dosimetry platform named RAPID and a three dimensional dose distribution in the phantom was estimated. Additionally, a GEANT4 benchmarking scenario (denoted 'idealized') was created using a stylized representation of the phantom. There was good agreement for all six probes, the differences between measurement and RAPID ranged between -5.5% and 0.9%. The difference between the measured and the idealized GEANT4 scenario was calculated and ranged from -4.3% and -20.5%. This work demonstrates good agreement between TLD measurements and RAPID. In addition, it introduces a novel TLD probe that can be easily introduced into clinical nuclear medicine workflows to provide QA of image-based dosimetry for RPT treatments.

Targeting of Head and Neck Cancer by Radioiodinated CLR1404 in Murine Xenograft Tumor Models with Partial Volume Corrected Theranostic Dosimetry.

Background: Delivery of radiotherapeutic dose to recurrent head and neck cancer (HNC) is primarily limited by locoregional toxicity in conventional radiotherapy. As such, HNC patients stand to benefit from the conformal targeting of primary and remnant disease achievable with radiopharmaceutical therapies. In this study, the authors investigated the tumor targeting capacity of 131I-CLR1404 (iopofosine I-131) in various HNC xenograft mouse models and the impact of partial volume correction (PVC) on theranostic dosimetry based on 124I-CLR1404 (CLR 124) positron emission tomography (PET)/computed tomography (CT) imaging. Methods: Mice bearing flank tumor xenograft models of HNC (six murine cell line and six human patient derived) were intravenously administered 6.5-9.1 MBq of CLR 124 and imaged five times over the course of 6 d using microPET/CT. In vivo tumor uptake of CLR 124 was assessed and PVC for 124I was applied using a novel preclinical phantom. Using subject-specific theranostic dosimetry estimations for iopofosine I-131 based on CLR 124 imaging, a discrete radiation dose escalation study (2, 4, 6, and 8 Gy) was performed to evaluate tumor growth response to iopofosine I-131 relative to a single fraction of external beam radiation therapy (6 Gy). Results: PET imaging demonstrated consistent tumor selective uptake and retention of CLR 124 across all HNC xenograft models. Peak uptake of 4.4% ± 0.8% and 4.2% ± 0.4% was observed in squamous cell carcinoma-22B and UW-13, respectively. PVC application increased uptake measures by 47%-188% and reduced absolute differences between in vivo and ex vivo uptake measurements from 3.3% to 1.0 percent injected activity per gram. Tumor dosimetry averaged over all HNC models was 0.85 ± 0.27 Gy/MBq (1.58 ± 0.46 Gy/MBq with PVC). Therapeutic iopofosine I-131 studies demonstrated a variable, but linear relationship between iopofosine I-131 radiation dose and tumor growth delay (p < 0.05). Conclusions: Iopofosine I-131 demonstrated tumoricidal capacity in preclinical HNC tumor models and the theranostic pairing with CLR 124 presents a promising new treatment approach for personalizing administration of iopofosine I-131.

Comparative Study of the Effect of Radiation Delivered by Lutetium-177 or Actinium-225 on Anti-GD2 Chimeric Antigen Receptor T Cell Viability and Functions.

BACKGROUND AND PURPOSE: Chimeric antigen receptor (CAR) T cells have been relatively ineffective against solid tumors. Low-dose radiation which can be delivered to multiple sites of metastases by targeted radionuclide therapy (TRT) can elicit immunostimulatory effects. However, TRT has never been combined with CAR T cells against solid tumors in a clinical setting. This study investigated the effects of radiation delivered by Lutetium-177 (177Lu) and Actinium-225 (225Ac) on the viability and effector function of CAR T cells in vitro to evaluate the feasibility of such therapeutic combinations. After the irradiation of anti-GD2 CAR T cells with various doses of radiation delivered by 177Lu or 225Ac, their viability and cytotoxic activity against GD2-expressing human CHLA-20 neuroblastoma and melanoma M21 cells were determined by flow cytometry. The expression of the exhaustion marker PD-1, activation marker CD69 and the activating receptor NKG2D was measured on the irradiated anti-GD2 CAR T cells. Both 177Lu and 225Ac displayed a dose-dependent toxicity on anti-GD2 CAR T cells. However, radiation enhanced the cytotoxic activity of these CAR T cells against CHLA-20 and M21 irrespective of the dose tested and the type of radionuclide. No significant changes in the expression of PD-1, CD69 and NKG2D was noted on the CAR T cells following irradiation. Given a lower CAR T cell viability at equal doses and an enhancement of cytotoxic activity irrespective of the radionuclide type, 177Lu-based TRT may be preferred over 225Ac-based TRT when evaluating a potential synergism between these therapies in vivo against solid tumors.

Validation of Monte Carlo 131 I radiopharmaceutical dosimetry workflow using a 3D-printed anthropomorphic head and neck phantom.

PURPOSE: Approximately 50% of head and neck cancer (HNC) patients will experience loco-regional disease recurrence following initial courses of therapy. Retreatment with external beam radiotherapy (EBRT) is technically challenging and may be associated with a significant risk of irreversible damage to normal tissues. Radiopharmaceutical therapy (RPT) is a potential method to treat recurrent HNC in conjunction with EBRT. Phantoms are used to calibrate and add quantification to nuclear medicine images, and anthropomorphic phantoms can account for both the geometrical and material composition of the head and neck. In this study, we present the creation of an anthropomorphic, head and neck, nuclear medicine phantom, and its characterization for the validation of a Monte Carlo, SPECT image-based, 131 I RPT dosimetry workflow. METHODS: 3D-printing techniques were used to create the anthropomorphic phantom from a patient CT dataset. Three 131 I SPECT/CT imaging studies were performed using a homogeneous, Jaszczak, and an anthropomorphic phantom to quantify the SPECT images using a GE Optima NM/CT 640 with a high energy general purpose collimator. The impact of collimator detector response (CDR) modeling and volume-based partial volume corrections (PVCs) upon the absorbed dose was calculated using an image-based, Geant4 Monte Carlo RPT dosimetry workflow and compared against a ground truth scenario. Finally, uncertainties were quantified in accordance with recent EANM guidelines. RESULTS: The 3D-printed anthropomorphic phantom was an accurate re-creation of patient anatomy including bone. The extrapolated Jaszczak recovery coefficients were greater than that of the 3D-printed insert (∼22.8 ml) for both the CDR and non-CDR cases (with CDR: 0.536 vs. 0.493, non-CDR: 0.445 vs. 0.426, respectively). Utilizing Jaszczak phantom PVCs, the absorbed dose was underpredicted by 0.7% and 4.9% without and with CDR, respectively. Utilizing anthropomorphic phantom recovery coefficient overpredicted the absorbed dose by 3% both with and without CDR. All dosimetry scenarios that incorporated PVC were within the calculated uncertainty of the activity. The uncertainties in the cumulative activity ranged from 23.6% to 106.4% for Jaszczak spheres ranging in volume from 0.5 to 16 ml. CONCLUSION: The accuracy of Monte Carlo-based dosimetry for 131 I RPT in HNC was validated with an anthropomorphic phantom. In this study, it was found that Jaszczak-based PVCs were sufficient. Future applications of the phantom could involve 3D printing and characterizing patient-specific volumes for more personalized RPT dosimetry estimates.

New capabilities of the Monte Carlo dose engine ARCHER-RT: Clinical validation of the Varian TrueBeam machine for VMAT external beam radiotherapy.

PURPOSE: The Monte Carlo radiation transport method is considered the most accurate approach for absorbed dose calculations in external beam radiation therapy. In this study, an efficient and accurate source model of the Varian TrueBeam 6X STx Linac is developed and integrated with a fast Monte Carlo photon-electron transport absorbed dose engine, ARCHER-RT, which is capable of being executed on CPUs, NVIDIA GPUs, and AMD GPUs. This capability of fast yet accurate radiation dose calculation is essential for clinical utility of this new technology. This paper describes the software and algorithmic developments made to the ARCHER-RT absorbed dose engine. METHODS: AMD's Heterogeneous-Compute Interface for Portability (HIP) was implemented in ARCHER-RT to allow for device independent execution on NVIDIA and AMD GPUs. Architecture-specific atomic-add algorithms have been identified and both more accurate single-precision and double-precision computational absorbed dose calculation methods have been added to ARCHER-RT and validated through a test case to evaluate the accuracy and performance of the algorithms. The validity of the source model and the radiation transport physics were benchmarked against Monte Carlo simulations performed with EGSnrc. Secondary dose-check physics plans, and a clinical prostate treatment plan were calculated to demonstrate the applicability of the platform for clinical use. Absorbed dose difference maps and gamma analyses were conducted to establish the accuracy and consistency between the two Monte Carlo models. Timing studies were conducted on a CPU, an NVIDIA GPU, and an AMD GPU to evaluate the computational speed of ARCHER-RT. RESULTS: Percent depth doses were computed for different field sizes ranging from 1.5 cm2  × 1.5 cm2 to 22 cm2  × 40cm2 and the two codes agreed for all points outside high gradient regions within 3%. Axial profiles computed for a 10 cm2  × 10 cm2 field for multiple depths agreed for all points outside high gradient regions within 2%. The test case investigating the impact of native single-precision compared to double-precision showed differences in voxels as large as 71.47% and the implementation of KAS single-precision reduced the difference to less than 0.01%. The 3%/3mm gamma pass rates for an MPPG5a multileaf collimator (MLC) test case and a clinical VMAT prostate plan were 94.2% and 98.4% respectively. Timing studies demonstrated the calculation of a VMAT plan was completed in 50.3, 187.9, and 216.8 s on an NVIDIA GPU, AMD GPU, and Intel CPU, respectively. CONCLUSION: ARCHER-RT is capable of patient-specific VMAT external beam photon absorbed dose calculations and its potential has been demonstrated by benchmarking against a well validated EGSnrc model of a Varian TrueBeam. Additionally, the implementation of AMD's HIP has shown the flexibility of the ARCHER-RT platform for device independent calculations. This work demonstrates the significant addition of functionality added to ARCHER-RT framework which has marked utility for both research and clinical applications and demonstrates further that Monte Carlo-based absorbed dose engines like ARCHER-RT have the potential for widespread clinical implementation.

Mercury in abiotic matrices of Clear Lake, California: human health and ecotoxicological implications.

Mercury (Hg) from Hg mining at Clear Lake, California, USA, has contaminated water and sediments for over 130 years and has the potential to affect human and environmental health. With total mercury (TotHg) concentrations up to 438 mg/kg (dry mass) in surficial sediments and up to 399 ng/L in lake water, Clear Lake is one of the most Hg-contaminated lakes worldwide. Particulate Hg in surface water near the mine ranges from 10,000 to 64,000 ng/g; TotHg declines exponentially with distance from the Sulphur Bank Mercury Mine. From 1992 to 1998, no significant long-term trends for TotHg or methylmercury (MeHg) in sediments or water were observed, but peaks of both TotHg and MeHg occurred following a 1995 flooding event. Sediments and water exhibit summer/fall maxima and winter/spring minima for MeHg, but not TotHg. Sediment TotHg has not declined significantly a decade after remediation in 1992. At the mine site, aqueous TotHg reached 374,000 ng/L in unfiltered groundwater. Pore water sulfate in sediments varies seasonally from 112 mg/L in summer/fall (when Hg methylation is highest) to 3300 mg/L in winter. While TotHg is exceptionally high in both sediments and water, MeHg is substantially lower than would be expected based on the bulk Hg loading to the lake and in comparison with other sites worldwide. Total mercury in Clear Lake water does not exceed the Safe Drinking Water Act criteria, but it sometimes greatly exceeds human health criteria established by the Great Lakes Initiative, U.S. Environmental Protection Agency water quality guidelines, and the California Toxics Rule criterion. Methylmercury concentrations exceed the Great Lakes Initiative criterion for MeHg in water at some sites only during summer/fall. Relative to ecological health, Clear Lake sediments greatly exceed the National Oceanic and Atmospheric Administration's benthic fauna Sediment Quality Guidelines for toxic effects, as well as the more concensus-based Threshold Effects Concentration criteria. Based on these criteria, Hg-contaminated sediments and water from Clear Lake are predicted to have some lethal and sublethal effects on specific resident aquatic species. However, based on unique physical and chemical characteristics of the Clear Lake environment, MeHg toxicity may be significantly less than anticipated from the large inorganic Hg loading.

Clear Lake sediments: anthropogenic changes in physical sedimentology and magnetic response.

We analyzed the sedimentological characteristics and magnetic properties of cores from the three basins of Clear Lake, California, USA, to assess the depositional response to a series of land use changes that occurred in the watershed over the 20th century. Results indicate that distinct and abrupt shifts in particle size, magnetic concentration/mineralogy, and redox conditions occur concurrently with a variety of ecological and chemical changes in lake bed sediments. This coincidence of events occurred around 1927, a datum determined by an abrupt increase in total mercury (Hg) in Clear Lake cores and the known initiation of open-pit Hg mining at the Sulphur Bank Mercury Mine, confirmed by 210Pb dating. Ages below the 1927 horizon were determined by accelerator mass spectrometry on 14C of coarse organic debris. Calculated sedimentation rates below the 1927 datum are approximately 1 mm/yr, whereas rates from 1927 to 2000 are up to an order of magnitude higher, with averages of approximately 3.5-19 mm/yr. In both the Oaks and Upper Arms, the post-1927 co-occurrence of abrupt shifts in magnetic signatures with color differences indicative of changing redox conditions is interpreted to reflect a more oxygenated diagenetic regime and rapid burial of sediment below the depth of sulfate diffusion. Post-1927 in the Oaks Arm, grain size exhibits a gradual coarsening-upward pattern that we attribute to the input of mechanically deposited waste rock related to open-pit mining activities at the mine. In contrast, grain size in the Upper Arm exhibits a gradational fining-upward after 1927 that we interpret as human-induced erosion of fine-grained soils and chemically weathered rocks of the Franciscan Assemblage by heavy earthmoving equipment associated with a road- and home-building boom, exacerbated by stream channel mining and wetlands destruction. The flux of fine-grained sediment into the Upper Arm increased the nutrient load to the lake, and that in turn catalyzed profuse cyanobacterial blooms through the 20th century. The resulting organic biomass, in combination with the increased inorganic sediment supply, contributed to the abrupt increase in sedimentation rate after 1927.

Mine-derived mercury: effects on lower trophic species in Clear Lake, California.

Considerable ecological research on mercury (Hg) has focused on higher trophic level species (e.g., fishes and birds), but less on lower trophic species. Clear Lake, site of the abandoned Sulphur Bank Mercury Mine, provides a unique opportunity to study a system influenced by mine-derived Hg. An exponentially decreasing gradient of total Hg (TotHg) away from the mine allowed us to evaluate Hg bioaccumulation in planktonic and benthic invertebrates and evaluate population- and community-level parameters that might be influenced by Hg. Studies from 1992-1998 demonstrated that TotHg in lower trophic species typically decreased exponentially away from the mine, similar to trends observed in water and sediments. However, a significant amount of invertebrate TotHg (approximately 60% for sediment-dwelling chironomid insect larvae) likely derives from Hg-laden particles in their guts. Spatially, whole-body methylmercury (MeHg) did not typically exhibit a significant decrease with increasing distance from the mine. Temporally, TotHg concentrations in plankton and chironomids did not exhibit any short-term (seasonal or annual) or long-term (multiyear) trends. Methylmercury, however, was elevated during late summer/fall in both plankton and chironomids, but it exhibited no long-term increase or decrease during this study. Although data from a 50-yr monitoring program for benthic chaoborid and chironomid larvae documented significant population fluctuations, they did not demonstrate population-level trends with respect to Hg concentrations. Littoral invertebrates also exhibited no detectable population- or community-level trends associated with the steep Hg gradient. Although sediment TotHg concentrations (1-1200 mg/kg dry mass) exceed sediment quality guidelines by up to 7000 times, it is notable that no population- or community-level effects were detected for benthic and planktonic taxa. In comparison with other sites worldwide, Clear Lake's lower trophic species typically have significantly higher TotHg concentrations, but comparable or lower MeHg concentrations, which may be responsible for the discrepancy between highly elevated TotHg concentrations and the general lack of observed population- or community-level effects. These data suggest that MeHg, as well as TotHg, should be used when establishing sediment quality guidelines. In addition, site-specific criteria should be established using the observed relationship between MeHg and observed ecological responses.

Spatiotemporal trends in fish mercury from a mine-dominated ecosystem: Clear Lake, California.

Clear Lake, California, USA, receives acid mine drainage and mercury (Hg) from the Sulphur Bank Mercury Mine, a U.S. Environmental Protection Agency (U.S. EPA) Superfund Site that was active intermittently from 1873 to 1957 and partially remediated in 1992. Mercury concentrations were analyzed primarily in four species of Clear Lake fishes: inland silversides (Menidia beryllina, planktivore), common carp (Cyprinus carpio, benthic scavenger/omnivore), channel catfish (Ictalurus punctatus, benthic omnivorous predator), and largemouth bass (Micropterus salmoides, piscivorous top predator). These data represent one of the largest fish Hg data sets for a single site, especially in California. Spatially, total Hg (TotHg) in silversides and bass declined with distance from the mine, indicating that the mine site represents a point source for Hg loading to Clear Lake. Temporally, fish Hg has not declined significantly over 12 years since mine site remediation. Mercury concentrations were variable throughout the study period, with no monotonic trends of increase or decrease, except those correlated with boom and bust cycles of an introduced fish, threadfin shad (Dorosoma petenense). However, stochastic events such as storms also influence juvenile largemouth bass Hg as evidenced during an acid mine drainage overflow event in 1995. Compared to other sites regionally and nationally, most fish in Clear Lake exhibit Hg concentrations similar to other Hg-contaminated sites, up to approximately 2.0 mg/kg wet mass (WM) TotHg in largemouth bass. However, even these elevated concentrations are less than would be anticipated from such high inorganic Hg loading to the lake. Mercury in some Clear Lake largemouth bass exceeded all human health fish consumption guidelines established over the past 25 years by the U.S. Food and Drug Administration (1.0 mg/kg WM), the National Academy of Sciences (0.5 mg/kg WM), and the U.S. EPA (0.3 mg/kg WM). Mercury in higher trophic level fishes exceeds ecotoxicological risk assessment estimates for concentrations that would be safe for wildlife, specifically the nonlisted Common Merganser and the recently delisted Bald Eagle. Fish populations of 11 out of 18 species surveyed exhibited a significant decrease in abundance with increasing proximity to the mine; this decrease is correlated with increasing water and sediment Hg. These trends may be related to Hg or other lake-wide gradients such as distribution of submerged aquatic vegetation.

The legacy of mercury cycling from mining sources in an aquatic ecosystem: from ore to organism.

Clear Lake is the site of an abandoned mercury (Hg) mine (active intermittently from 1873 to 1957), now a U.S. Environmental Protection Agency Superfund Site. Mining activities, including bulldozing waste rock and tailings into the lake, resulted in approximately 100 Mg of Hg entering the lake's ecosystem. This series of papers represents the culmination of approximately 15 years of Hg-related studies on this ecosystem, following Hg from the ore body to the highest trophic levels. A series of physical, chemical, biological, and limnological studies elucidate how ongoing Hg loading to the lake is influenced by acid mine drainage and how wind-driven currents and baroclinic circulation patterns redistribute Hg throughout the lake. Methylmercury (MeHg) production in this system is controlled by both sulfate-reducing bacteria as well as newly identified iron-reducing bacteria. Sediment cores (dated with dichlorodiphenyldichlorethane [DDD], 210pb, and 14C) to approximately 250 cm depth (representing up to approximately 3000 years before present) elucidate a record of total Hg (TotHg) loading to the lake from natural sources and mining and demonstrate how MeHg remains stable at depth within the sediment column for decades to millenia. Core data also identify other stresses that have influenced the Clear Lake Basin especially over the past 150 years. Although Clear Lake is one of the most Hg-contaminated lakes in the world, biota do not exhibit MeHg concentrations as high as would be predicted based on the gross level of Hg loading. We compare Clear Lake's TotHg and MeHg concentrations with other sites worldwide and suggest several hypotheses to explain why this discrepancy exists. Based on our data, together with state and federal water and sediment quality criteria, we predict potential resulting environmental and human health effects and provide data that can assist remediation efforts.