VOXEL-LEVEL ABSORBED DOSE CALCULATIONS WITH A DETERMINISTIC GRID-BASED BOLTZMANN SOLVER FOR NUCLEAR MEDICINE AND THE CLINICAL VALUE OF VOXEL-LEVEL CALCULATIONS

Voxel-level absorbed dose (VLAD) is rarely calculated for nuclear medicine (NM) procedures involving unsealed sources or 90Y microspheres (YM). The current standard of practice for absorbed dose calculations in NM utilizes MIRD S-values, which 1) assume a uniform distribution in organs, 2) do not use patient specific geometry, and 3) lack a tumor model. VLADs overcome these limitations. One reason VLADs are not routinely performed is the difficulty in obtaining accurate absorbed doses in a clinically acceptable time. The deterministic grid-based Boltzmann solver (GBBS) was recently applied to radiation oncology where it was reported as fast and accurate for both megavoltage photons and high dose rate nuclide-based photon brachytherapy. This dissertation had two goals. The first was to demonstrate that the general GBBS code ATTILA™ can be used for VLADs in NM, where primary photon and electron sources are distributed throughout a patient. The GBBS was evaluated in voxel-S-value geometries where agreement with Monte Carlo (MC) in the source voxel was 6% for 90Y and 131I; 20% differences were seen for mono-energetic 10 keV photons in bone. An adaptive tetrahedral mesh (ATM) generation procedure was developed using information from both the SPECT and CT for 90Y and 131I patients. The ATM with increased energy transport cutoffs, enabled GBBS transport to execute in under 2 (90Y) and 10 minutes (131I). GBBS absorbed doses to tumors and organs were within 4.5% of MC. Dose volume histograms were indistinguishable from MC. The second goal was to demonstrate VLAD value using 21 YM patients. Package insert dosimetry was not able to predict mean VLAD tumor absorbed doses. Partition model had large bias (factor of 0.39) and uncertainty (±128 Gy). Dose-response curves for hepatocellular carcinoma tumors were generated using logistic regression. The dose covering 70% of volume (D70) predicted binary modified RECIST response with an area under the curve of 80.3%. A D70 88 Gy threshold yielded 89% specificity and 69% sensitivity. The GBBS was shown to be fast and accurate, flaws in clinical dosimetry models were highlighted, and dose-response curves were generated. The findings in this dissertation support the adoption of VLADs in NM

Voxel-based partial volume correction for accurate quantitative voxel values

Purpose: The accuracy of voxelized information in emission imaging is limited by spatial resolution (FWHM = 2.35σ) producing biases for objects smaller than 3 FWHM. If the signal distribution is non‐uniform within 3σ of the voxel of interest then equilibrium does not exist and partial volume effect (PVE) compromises voxel accuracy. We propose a mathematical model to improve the accuracy of quantitative images of arbitrary distribution by bounding true voxel signal and estimating PVE for each voxel.Methods: A monotonically increasing parametric dataset is created for each voxel of an emission image by radial integration from the voxel center to radius = 6σ. Each cumulative integration plot from r = 3σ to 6σ is fit to a function A*4π /3*r3 + B*ΔV derived assuming a local uniform signal distribution (A) where ΔV is the voxel volume. The constant BΔV represents the converged within 3σ integral of PVE. B > 0 implies spill‐out, B < 0 spill‐in, and B = 0 no PVE. We tested the proposed model on simulations of 1D&2D datasets containing known signal distributions and 18F‐PET/CT images of a 6cc lung lesion and bladder.Results: Signal accuracy was > 99% in simulated 1D & 2D datasets. For the tumor, the original maximum value was 10kBq/ml. We obtained A = 3.5kBq/ml and B = 14kBq/ml for a total of 17.7kBq/ml. This yields (A+B)/original = 1.8 indicating substantial spill‐out of ~80% and a large error for the original voxel value. For a voxel in the center of the bladder, the original value was 46kBq/ml with A = 44kBq/ml, B = 7kBq/ml. (A+B)/original = 1.11 indicating near‐equilibrium at center of bladder and low spill-out of ~11% as expected. Local signal images (A) resemble low‐pass filtered original image and (B) shows the magnitude and direction of PVE. Conclusion: A new mathematical model to estimate the accuracy of voxels in quantitative images of arbitrary distribution has been developed. Analysis of additional patients is underway.-------------------------------------Cite this article as: Mikell J, Kappadath SC. Voxel-based partial volume correction for accurate quantitative voxel values. Int J Cancer Ther Oncol 2014; 2(2):020229. DOI: 10.14319/ijcto.0202.2

CalYOUTH Survey of Young Adults' Child Welfare Workers

This report presents the results of the CalYOUTH Survey of Young Adults' Child Welfare Workers, a survey of case workers supervising youth in extended foster care who are participating in the CalYOUTH Youth Survey. The report shares the county child welfare workers' views on how these young people are faring with the transition to adulthood, as well as their preparedness and service needs in a wide range of areas. The report also shares workers' perceptions of the availability and helpfulness of services within their county, their perceptions of court personnel's supportiveness of extended care, their satisfaction with collaboration with other systems of potential support for youth, and their views of challenges to effective implementation of extended foster care in California. The survey results highlight areas of progress and opportunities for continued improvement as California continues its development of foster care for young adults

Findings from the California Youth Transitions to Adulthood Study (CalYOUTH): Conditions of Youth at Age 19

The "CalYOUTH Wave 2 Youth Survey", conducted when the young people participating in CalYOUTH were 19 years old, follows up on a survey of the same young people when they were approaching the age of majority in California's foster care system. More than 80 percent of the youth who took part in the baseline interviews participated in the Wave 2 survey. The report provides the most comprehensive view to date of young adults making the transition to adulthood from foster care in California, highlighting differences between young people participating in extended foster care and young people who had left care. The report provides feedback for all parties interested in improving youth's transitions from foster care to adulthood

Dose volume histogram‐based optimization of image reconstruction parameters for quantitative 90Y‐PET imaging

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147185/1/mp13269.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147185/2/mp13269_am.pd

Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry

Purpose: Dosimetry for 90Y microsphere therapies (YMT) with Standard (SM) and Partition (PM) models provide only uniform dose estimates to tumor and liver. Our objective is to calculate tumor dose heterogeneity, known to effect response, using voxel-based dosimetry and investigate the limitations of SM and PM.Methods: Voxel-based dosimetry was performed on 17 YMT patients using Monte Carlo DOSXYZnrc. 90Y activity and tissue/density distributions were based on quantitative 90Y bremsstrahlung SPECT/CT. Tumors (n=31), liver, and treatment lobe/segments were segmented on diagnostic CT or MR. Dose volume histograms (DVH) were created for tumors and normal liver. Bland-Altman analysis compared voxel-based mean absorbed doses to tumor and liver with SM and PM. Tumor and normal liver absorbed dose heterogeneity were investigated through metrics: integral uniformity (IU), D10/D90, COV. Correlations of heterogeneity with voxel-based mean doses and volumes were evaluated.Results: Heterogeneity metrics (mean ± 1σ) for tumor dose were COV = 0.48 ± 0.28, D10/D90 = 4.7 ± 3.9, and IU = 0.8 ± 0.18. Heterogeneity metrics correlated with tumor volume (r > 0.58) but not tumor mean doses (r < 0.20). Voxel-based tumor mean doses correlated with PM (r = 0.84) but not SM (r = 0.08). Both yielded poor limits of agreement with of 83 ± 174 and -28 ± 181 Gy, respectively. Normal liver heterogeneity metrics (mean ± 1σ) were COV = 0.83 ± 0.29, D10/D90 = 12 ± 15, and IU = 0.97 ± 0.03. Only D10/D90 (r = 0.49) correlated with mean normal liver absorbed dose. Voxel-based normal liver/lobe mean doses correlated with PM (r = 0.96), but had poor limits of agreement (26 ± 29 Gy).Conclusion: Tumor doses have high levels of heterogeneity that increase with volume but are independent of dose. Voxel-based DVH and dose heterogeneity metrics will promote accurate characterization of tumor response following YMT.--------------------------------------Cite this article as: Mikell J, Mourtada F, Mahvash A, Kappadath SC. Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry. Int J Cancer Ther Oncol 2014; 2(2):020228. DOI: 10.14319/ijcto.0202.2

The value of 99mTc-MAA SPECT/CT for lung shunt estimation in 90Y radioembolization: a phantom and patient study

Abstract Background A major toxicity concern in radioembolization therapy of hepatic malignancies is radiation-induced pneumonitis and sclerosis due to hepatopulmonary shunting of 90Y microspheres. Currently, 99mTc macroaggregated albumin (99mTc-MAA) imaging is used to estimate the lung shunt fraction (LSF) prior to treatment. The aim of this study was to evaluate the accuracy/precision of LSF estimated from 99mTc planar and SPECT/CT phantom imaging, and within this context, to compare the corresponding LSF and lung-absorbed dose values from 99mTc-MAA patient studies. Additionally, LSFs from pre- and post-therapy imaging were compared. Results A liver/lung torso phantom filled with 99mTc to achieve three lung shunt values was scanned by planar and SPECT/CT imaging with repeat acquisitions to assess accuracy and precision. To facilitate processing of patient data, a workflow that relies on SPECT and CT-based auto-contouring to define liver and lung volumes for the LSF calculation was implemented. Planar imaging-based LSF estimates for 40 patients, obtained from their medical records, were retrospectively compared with SPECT/CT imaging-based calculations with attenuation and scatter correction. Additionally, in a subset of 20 patients, the pre-therapy estimates were compared with 90Y PET/CT-based measurements. In the phantom study, improved accuracy in LSF estimation was achieved using SPECT/CT with attenuation and scatter correction (within 13% of the true value) compared with planar imaging (up to 44% overestimation). The results in patients showed a similar trend with planar imaging significantly overestimating LSF compared to SPECT/CT. There was no correlation between lung shunt estimates and the delay between 99mTc-MAA administration and scanning, but off-target extra hepatic uptake tended to be more likely in patients with a longer delay. The mean lung absorbed dose predictions for the 28 patients who underwent therapy was 9.3 Gy (range 1.3–29.4) for planar imaging and 3.2 Gy (range 0.4–13.4) for SPECT/CT. For the patients with post-therapy imaging, the mean LSF from 90Y PET/CT was 1.0%, (range 0.3–2.8). This value was not significantly different from the mean LSF estimate from 99mTc-MAA SPECT/CT (mean 1.0%, range 0.4–1.6; p = 0.968), but was significantly lower than the mean LSF estimate based on planar imaging (mean 4.1%, range 1.2–15.0; p = 0.0002). Conclusions The improved accuracy demonstrated by the phantom study, agreement with 90Y PET/CT in patient studies, and the practicality of using auto-contouring for liver/lung definition suggests that 99mTc-MAA SPECT/CT with scatter and attenuation corrections should be used for lung shunt estimation prior to radioembolization.https://deepblue.lib.umich.edu/bitstream/2027.42/144504/1/13550_2018_Article_402.pd

The impact of a high‐definition multileaf collimator for spine SBRT

PurposeAdvanced radiotherapy delivery systems designed for high‐dose, high‐precision treatments often come equipped with high‐definition multi‐leaf collimators (HD‐MLC) aimed at more finely shaping radiation dose to the target. In this work, we study the effect of a high definition MLC on spine stereotactic body radiation therapy (SBRT) treatment plan quality and plan deliverability.Methods and MaterialsSeventeen spine SBRT cases were planned with VMAT using a standard definition MLC (M120), HD‐MLC, and HD‐MLC with an added objective to reduce monitor units (MU). M120 plans were converted into plans deliverable on an HD‐MLC using in‐house software. Plan quality and plan deliverability as measured by portal dosimetry were compared among the three types of plans.ResultsOnly minor differences were noted in plan quality between the M120 and HD‐MLC plans. Plans generated with the HD‐MLC tended to have better spinal cord sparing (3% reduction in maximum cord dose). HD‐MLC plans on average had 12% more MU and 55% greater modulation complexity as defined by an in‐house metric. HD‐MLC plans also had significantly degraded deliverability. Of the VMAT arcs measured, 94% had lower gamma passing metrics when using the HD‐MLC.ConclusionModest improvements in plan quality were noted when switching from M120 to HD‐MLC at the expense of significantly less accurate deliverability in some cases.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139989/1/acm212197.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139989/2/acm212197_am.pd

Impact of 90Y PET gradient-based tumor segmentation on voxel-level dosimetry in liver radioembolization

Abstract Background The purpose was to validate 90Y PET gradient-based tumor segmentation in phantoms and to evaluate the impact of the segmentation method on reported tumor absorbed dose (AD) and biological effective dose (BED) in 90Y microsphere radioembolization (RE) patients. A semi-automated gradient-based method was applied to phantoms and patient tumors on the 90Y PET with the initial bounding volume for gradient detection determined from a registered diagnostic CT or MR; this PET-based segmentation (PS) was compared with radiologist-defined morphologic segmentation (MS) on CT or MRI. AD and BED volume histogram metrics (D90, D70, mean) were calculated using both segmentations and concordance/correlations were investigated. Spatial concordance was assessed using Dice similarity coefficient (DSC) and mean distance to agreement (MDA). PS was repeated to assess intra-observer variability. Results In phantoms, PS demonstrated high accuracy in lesion volumes (within 15%), AD metrics (within 11%), high spatial concordance relative to morphologic segmentation (DSC > 0.86 and MDA  0.99, MDA < 0.2 mm, AD/BED metrics within 2%). For patients (58 lesions), spatial concordance between PS and MS was degraded compared to in-phantom (average DSC = 0.54, average MDA = 4.8 mm); the average mean tumor AD was 226 ± 153 and 197 ± 138 Gy, respectively for PS and MS. For patient AD metrics, the best Pearson correlation (r) and concordance correlation coefficient (ccc) between segmentation methods was found for mean AD (r = 0.94, ccc = 0.92), but worsened as the metric approached the minimum dose (for D90, r = 0.77, ccc = 0.69); BED metrics exhibited a similar trend. Patient PS showed low intra-observer variability (average DSC = 0.81, average MDA = 2.2 mm, average AD/BED metrics within 3.0%). Conclusions 90Y PET gradient-based segmentation led to accurate/robust results in phantoms, and showed high concordance with MS for reporting mean tumor AD/BED in patients. However, tumor coverage metrics such as D90 exhibited worse concordance between segmentation methods, highlighting the need to standardize segmentation methods when reporting AD/BED metrics from post-therapy 90Y PET. Estimated differences in reported AD/BED metrics due to segmentation method will be useful for interpreting RE dosimetry results in the literature including tumor response data.https://deepblue.lib.umich.edu/bitstream/2027.42/146544/1/40658_2018_Article_230.pd

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction