Luke Arentsen

Water-fat MRI for assessing changes in bone marrow composition due to radiation and chemotherapy in gynecologic cancer patients.

To assess the feasibility of using fat‐fraction imaging for measuring marrow composition changes over large regions in patients undergoing cancer therapy.

Validation of marrow fat assessment using noninvasive imaging with histologic examination of human bone samples

PURPOSE The marrow composition throughout the body is heterogeneous and changes with age. Due to heterogeneity, invasive biopsies of the iliac crest do not truly represent the complete physiological status, impeding the clinical effectiveness of this method. Therefore, we aim to provide verification for an in vivo imaging technique using co-registered histologic examinations for assessment of marrow adiposity. METHODS Five recently expired (i.e. <24h) human cadavers were scanned with a dual source CT (DECT) scanner in order to measure marrow fat in the lumbar vertebrae. These donors were also imaged using water-fat MRI (wfMRI) which was used to estimate the fraction of yellow marrow. After imaging, lumbar columns were excised and the superior and inferior aspects of 21 vertebrae were removed. The remaining center section was processed for histological examination to find the ratio of adipocyte volume per tissue volume (AV/TV). RESULTS Results of DECT and wfMRI had a high correlation (r = 0.88). AV/TV ranged from 0.18 to 0.75 with a mean (SD) of 0.36 (0.18). Inter-evaluator reliability for AV/TV was r > 0.984. There were similar correlations between AV/TV and the imaging modalities, DECT-derived MF and wfMRI (r = 0.802 and 0.772, respectively). CONCLUSIONS A high MF variation was seen among the 25 vertebrae imaged. Both DECT and wfMRI have a good correlation with the histologic adipocyte proportion and can be used to measure MF. This makes longitudinal studies possible without painful, less-effective, invasive biopsies.

A phase I feasibility study of multi-modality imaging assessing rapid expansion of marrow fat and decreased bone mineral density in cancer patients ☆

PURPOSE Cancer survivors are at an increased risk for fractures, but lack of effective and economical biomarkers limits quantitative assessments of marrow fat (MF), bone mineral density (BMD) and their relation in response to cytotoxic cancer treatment. We report dual energy CT (DECT) imaging, commonly used for cancer diagnosis, treatment and surveillance, as a novel biomarker of MF and BMD. METHODS We validated DECT in pre-clinical and phase I clinical trials and verified with water-fat MRI (WF-MRI), quantitative CT (QCT) and dual-energy X-ray absorptiometry (DXA). Basis material composition framework was validated using water and small-chain alcohols simulating different components of bone marrow. Histologic validation was achieved by measuring percent adipocyte in the cadaver vertebrae and compared with DECT and WF-MRI. For a phase I trial, sixteen patients with gynecologic malignancies (treated with oophorectomy, radiotherapy or chemotherapy) underwent DECT, QCT, WF-MRI and DXA before and 12months after treatment. BMD and MF percent and distribution were quantified in the lumbar vertebrae and the right femoral neck. RESULTS Measured precision (3mg/cm(3)) was sufficient to distinguish test solutions. Adiposity in cadaver bone histology was highly correlated with MF measured using DECT and WF-MRI (r=0.80 and 0.77, respectively). In the clinical trial, DECT showed high overall correlation (r=0.77, 95% CI: 0.69, 0.83) with WF-MRI. MF increased significantly after treatment (p<0.002). Chemotherapy and radiation caused greater increases in MF than oophorectomy (p<0.032). L4 BMD decreased 14% by DECT, 20% by QCT, but only 5% by DXA (p<0.002 for all). At baseline, we observed a statistically significant inverse association between MF and BMD which was dramatically attenuated after treatment. CONCLUSION Our study demonstrated that DECT, similar to WF-MRI, can accurately measure marrow adiposity. Both imaging modalities show rapid increase in MF following cancer treatment. Our results suggest that MF and BMD cannot be used interchangeably to monitor skeletal health following cancer therapy.

Spatial and temporal fracture pattern in breast and gynecologic cancer survivors.

Objective(s): To assess skeletal wide fracture location and time of fracture after cancer treatment Study Design: One hundred thirty-nine women diagnosed with breast or gynecologic cancer between 2003 and 2012 that subsequently had a radiologic diagnosis of fracture were identified retrospectively using electronic medical records. Results were compared with skeletal fracture pattern previously reported for a general population. Results: Skeletal fractures in cancer patients occur throughout the entire skeleton similar to general population. The most common sites were vertebrae (16%), feet and toes (15%), ribs (12%), hands and fingers (10%), and pelvis (8%). Fracture incidence was observed starting within the first year of survivorship, and continued to after five years. The median time from cancer diagnosis to fracture varied by age (p<0.01), from a high of 3.2 years for ages 50-59 to a low of 1.2 years for patients older than 70. Conclusion: The pattern of skeletal fracture is similar between cancer survivor and general population. Contrary to general assumption, survivors can experience skeletal fracture early after cancer treatment, especially at an older age. Thus, cancer survivorship care should include assessment of early time points with improved management of cancer treatment related bone injury.

Longitudinal FDG-PET Revealed Regional Functional Heterogeneity of Bone Marrow, Site-Dependent Response to Treatment and Correlation with Hematological Parameters

Purpose: The purposes of this study were: 1) to show bone marrow (BM) functional heterogeneity, 2) to demonstrate site-dependent responses of BM to cancer treatment utilizing whole body FDG-PET/CT and 3) to identify correlations between FDG uptake in different bone sites and long term complete blood count (CBC). Methods: Thirty two patients who had pre- and post-treatment FDG-PET/CT scans were selected retrospectively. Each patient received either head and neck radiation for cancer of the tongue, or pelvic radiation for rectal or cervical cancer with chemotherapy. Patients had FDG-PET/CT performed prior to the first radiation therapy session and at least one FDG-PET/CT after completion of the prescribed radiation therapy. Results: FDG uptake before radiotherapy was significantly different among bone regions (p < 0.01). This heterogeneity was felt to reflect site-dependent amounts of BM contents possibly due to structural and functional requirements. FDG uptake in the irradiated regions was significantly decreased on the first and second follow-ups after radiation. Feasibly, this could be due to a reduction in the number of active BM cells following intensive radiation in addition to concurrent chemotherapy. Overall, CBC significantly decreased after treatment. Correlation values of each hematological parameter with FDG uptake varied among skeletal regions and scan time points. FDG uptake in sacrum and lumbar regions had better correlation with white blood cells and neutrophils. Conclusions: Longitudinal FDG-PET revealed a regional functional heterogeneity of the BM site-dependent response to treatment. Patients experienced immediate and prolonged marrow metabolic damage that correlates with hematological parameters. FDG-PET/CT may provide additional capabilities to assess BM health.

Characterization of Rotating Gantry Micro-CT Configuration for the In Vivo Evaluation of Murine Trabecular Bone

The objective of this study is to determine the optimal physical parameters of a rotating gantry micro-CT system to assess in vivo changes to the trabecular bone of mice. Magnification, binning, peak kilovoltage, beam filtration, and tissue thickness are examined on a commercially available micro-CT system. The X-ray source and detector geometry provides 1.3×, 1.8×, or 3.3× magnification. Binning is examined from no binning to 2 to 4. Energy is varied from 40 to 80 kVp in 10 kVp increments and filter thickness is increased from no filtration to 1.5 mmAl in 0.5 mmAl increments. Mice are imaged at different magnifications and binning combinations to evaluate changes to image quality and microstructure estimation. Increasing magnification from 1.3× to 3.3× and lowering binning from 4 to 1 varies the spatial resolution from 2.5 to 11.8 lp/mm. Increasing the beam energy or filtration thickness decreases Hounsfield unit (HU) estimation, with a maximum rate of change being -286 HU/kVp for 80 kVp. Images for murine trabecular bone are blurred at effective pixel sizes above 60 μm. By comparing resolution, signal-to-noise ratio, and radiation dose, we find that a 3.3× magnification, binning of 2.80 kVp beam with a 0.5 mmAl filter comprises the optimal parameters to evaluate murine trabecular bone for this rotating gantry micro-CT.

SU-F-T-74: Experimental Validation of Monaco Electron Monte Carlo Dose Calculation for Small Fields

PURPOSE To verify experimentally the accuracy of Monaco (Elekta) electron Monte Carlo (eMC) algorithm to calculate small field size depth doses, monitor units and isodose distributions. METHODS Beam modeling of eMC algorithm was performed for electron energies of 6, 9, 12 15 and 18 Mev for a Elekta Infinity Linac and all available (6, 10, 14 20 and 25 cone) applicator sizes. Electron cutouts of incrementally smaller field sizes (20, 40, 60 and 80% blocked from open cone) were fabricated. Dose calculation was performed using a grid size smaller than one-tenth of the R80-20 electron distal falloff distance and number of particle histories was set at 500,000 per cm2 . Percent depth dose scans and beam profiles at dmax, d90 and d80 depths were measured for each cutout and energy with Wellhoffer (IBA) Blue Phantom2 scanning system and compared against eMC calculated doses. RESULTS The measured dose and output factors of incrementally reduced cutout sizes (to 3cm diameter) agreed with eMC calculated doses within ± 2.5%. The profile comparisons at dmax, d90 and d80 depths and percent depth doses at reduced field sizes agreed within 2.5% or 2mm. CONCLUSION Our results indicate that the Monaco eMC algorithm can accurately predict depth doses, isodose distributions, and monitor units in homogeneous water phantom for field sizes as small as 3.0 cm diameter for energies in the 6 to 18 MeV range at 100 cm SSD. Consequently, the old rule of thumb to approximate limiting cutout size for an electron field determined by the lateral scatter equilibrium (E (MeV)/2.5 in centimeters of water) does not apply to Monaco eMC algorithm.

SU-F-T-641: Comparative Study On Planning and Delivery Efficiency of Volumetric Modulated Arc Therapy Between Varian and Elekta Platforms for SBRT Lung Treatment

PURPOSE To compare the plan quality between Eclipse (Varian) and Monaco (Elekta) TPS. To ascertain, if SBRT lung treatment could be delivered in a single coplanar arc (360 degrees) with both Elekta and Varian platforms. To assess if the smaller leaf width in Varian Millennium and Elekta Agility MLC heads have a dosimetric advantage over Elekta MLCi2 head METHODS: Ten SBRT lung patients (PTV volumes ranging from 11 cc to 103cc) who were previously treated on Varian Linac with non-coplanar arcs and received 50Gy in 5 fractions were chosen for this study. The patients were replanned in Eclipse TPS (AAA algorithm) using a 360 degree coplanar single arc (SA) delivery technique and 2 partial complimentary 180 degree arcs (PA). Treatment planning using single coplanar arc (360 degree arc) was also done on Monaco TPS (Montecarlo) for both Agility (160 leaf) and MLCi2 (80 leaf) Elekta MLC heads RESULTS: The average monitor units to deliver 10 Gy across all delivery methods were 3000 ± 474 MU and did not vary with PTV size. Coplanar single arc and partial arc techniques did not compromise either the RTOG 0813 or 0915 low dose spillage criteria for R50% or the maximum dose to any point 2cm away from the PTV. OAR doses to spinal cord, heart, great vessels, esophagus, rib and lung were comparable on both Eclipse (Varian) and Monaco (Elekta) platforms regardless of the delivery method. CONCLUSION SBRT lung tumors can be treated with a single coplanar 360 degree arc in both Varian and Elekta platforms. Non coplanar arcs and increasing arc degrees more than 360 degrees had no benefit in this study regardless of the volume of PTV. 0.5 cm leaf width used in Millennium and Agility MLC heads had no significant dosimetric improvement over 1 cm leaves in the MLCi2 head.

SU-E-T-214: Comparison of Treatment Techniques for Dupuytren's Contracture and Risk Assessment of Normal Tissue Complications

Purpose: Duputren’s contracture (DC) is a benign disease characterized by abnormal thickening of the fascial surfaces of the hands or feet causing curling of the surface, functional impairment, weakness, and pain. The purpose of the investigation is to describe the radiation treatment approaches, compare these techniques, and discuss the potential side effects and complications of these techniques. Methods: Early stage DC has been treated with 120 kVp X rays but also with high-energy electrons or photons. High-energy electrons have been the radiation of choice but severe contracture of the hand makes it difficult to produce a plan with acceptable dose uniformity. High-energy photons can overcome this difficulty either by directing a beam onto the palmer or back of the surface of the hand, including bolus to maximize the surface dose. We calculated the dose to the bone for the 120 kVp treatment using published %DD data and mass energy absorption coefficients for bone and muscle. Results: The dose to underlying bone from megavoltage photons and electrons is essentially the same, but dose to the bone for using 120 kVp can be 4–5 times greater due to the photoelectric effect. For the 30 Gy dose deliver using this technique, the dose to the bone could be 84–105 Gy after taking the penetration of the beam into account. After radiotherapy, there is often decreased osteoblastic activity and vascular fibrosis that leads to osteitis, atrophy, and decreased metabolic bone activity. Incidence of fractures occurs routinely above 60 Gy with higher doses potentially leading to higher incidences of bone complications. Conclusion: Radiation therapy for DC using low-energy X rays can deliver a prohibitively high dose to the underlying bone potentially leading to severe bone complications.

SU‐C‐144‐02: Early Time Effect of Local Radiation On Entire Normal Bone Marrow

PURPOSE To investigate early time effect of local radiation on the entire normal bone marrow through microPET. METHODS Six 16 week-old BALB/c female intact mice were used for this study. PET acquisition with 18F-FDG was performed on day 2 after 16 Gy of local irradiation to both hind legs while other regions were completely shielded with lead. The delivered dose was verified with TLD and EBT3 film. Inveon small animal scanner (Siemens) was used for microPET scanning. The mean dose of 1 8 F-FDG was 18.8 ± 1.6 MBq. The scan was started at 30 minutes after the injection under anesthesia. About 10 μl of a whole blood sample from the tail vein was taken after the end of the scan. OSEM3D/FastMAP was used for the reconstruction. There are eight region of interest: skull, mandible, humerus, cervical, thoracic, lumber, femur and tibia. The SUV value was normalized by the blood activity to consider individual biological decay difference and compensate injection fluctuation for each mouse. The uptake change in 1 8 F-FDG before and after radiation was analyzed by mixed effects ANOVA, conducted using SAS proc mixed (version 9.2). RESULTS Radiation decreases 1 8 F-FDG uptake over the all regions (< 0.0001) on day 2 after irradiation. Though the degree of change is different individually, the uptake after irradiation is 46% of its pre-radiation level. The degree of 1 8 F-FDG uptake of pre-and post-radiation differs among the bony regions (< 0.0001). The irradiated region, especially the tibia, significantly changes 18F-FDG uptake, which is 29% of its pre-radiation level. The uptake pattern over the bony regions is changed before and after irradiation. CONCLUSION Local radiation changes 18F-FDG uptake of entire skeleton in this experimental rodent model suggesting that bone marrow functions are significantly affected by the local radiation at an early time point. FUNDING R01; Fund: 3002; DeptID: 11328; PCBU: UMSPR; Project: 00021280; Activity: 1.