Radiotherapy Response Using Intravoxel Incoherent Motion Magnetic Resonance Imaging in Liver Patients Treated with Stereotactic Body Radiotherapy

Magnetic resonance imaging is utilized as an important tool in radiation oncology for delineation of healthy and cancerous tissues, and evaluating the functionality of those tissues, structures, and organs. Currently, the clinical imaging protocol at Virginia Commonwealth University includes anatomical imaging for tissue and structure delineation, and to observe treatment induced changes. Diffusion weighted imaging (DWI) is also acquired for calculation of apparent diffusion coefficient (ADC) values to provide quantitative information on tissue diffusivity and microstructure. However, anatomical images and ADC values may not display the true extent of changes in tissue. This work seeks to further utilize the capabilities of MRI and expand its role in treatment response monitoring for liver cancer patients treated with stereotactic body radiotherapy (SBRT). To do so, an imaging protocol and image analysis methodology to evaluate treatment changes on pre- and post-treatment image sets was developed. An extension of DWI, termed intravoxel incoherent motion (IVIM) imaging, was utilized to quantitatively assess levels of perfusion and diffusion within the liver and tumor. Acquisition of high-quality diffusion weighted images of the liver necessitated the development of an MR safe respiratory motion management device, which was designed, constructed and evaluated in this work. An imaging protocol was developed providing anatomical and functional images of the liver, acquired under breath hold, utilizing the respiratory motion management device. An IVIM parameter calculation and texture analysis workflow was developed using MATLAB, and applied to acquired data sets from multiple studies, including past clinical cases, investigator, healthy volunteer, and liver cancer patient . Differences in IVIM and texture analysis parameters were investigated for healthy and diseased tissue, and for select dose regions from pre- and post-treatment imaging sessions. Significant differences, at a voxel level, were found between healthy and diseased tissue, and pre- and post-treatment volumes, for multiple parameters, including apparent diffusion coefficient, pure diffusion, and perfusion, as well as for various texture features. Overall, this study showed the potential of IVIM and texture analysis to be used for discriminating between healthy and diseased tissues in the liver, and for indication of treatment response

Monitoring Frequency of Intra‐Fraction Patient Motion Using the ExacTrac System for LINAC‐based SRS Treatments

Purpose: The aim of this study was to investigate the intra‐fractional patient motion using the ExacTrac system in LINAC‐based stereotactic radiosurgery (SRS). Method: A retrospective analysis of 104 SRS patients with kilovoltage image‐guided setup (Brainlab ExacTrac) data was performed. Each patient was imaged pre‐treatment, and at two time points during treatment (1st and 2nd mid‐treatment), and bony anatomy of the skull was used to establish setup error at each time point. The datasets included the translational and rotational setup error, as well as the time period between image acquisitions. After each image acquisition, the patient was repositioned using the calculated shift to correct the setup error. Only translational errors were corrected due to the absence of a 6D treatment table. Setup time and directional shift values were analyzed to determine correlation between shift magnitudes as well as time between acquisitions. Results: The average magnitude translation was 0.64 ± 0.59 mm, 0.79 ± 0.45 mm, and 0.65 ± 0.35 mm for the pre‐treatment, 1st mid‐treatment, and 2nd mid‐treatment imaging time points. The average time from pre‐treatment image acquisition to 1st mid‐treatment image acquisition was 7.98 ± 0.45 min, from 1st to 2nd mid‐treatment image was 4.87 ± 1.96 min. The greatest translation was 3.64 mm, occurring in the pre‐treatment image. No patient had a 1st or 2nd mid‐treatment image with greater than 2 mm magnitude shifts. Conclusion: There was no correlation between patient motion over time, in direction or magnitude, and duration of treatment. The imaging frequency could be reduced to decrease imaging dose and treatment time without significant changes in patient position

Biodistribution and PET Imaging of pharmacokinetics of manganese in mice using Manganese-52

<div><p>Manganese is essential to life, and humans typically absorb sufficient quantities of this element from a normal healthy diet; however, chronic, elevated ingestion or inhalation of manganese can be neurotoxic, potentially leading to <i>manganism</i>. Although imaging of large amounts of accumulated Mn(II) is possible by MRI, quantitative measurement of the biodistribution of manganese, particularly at the trace level, can be challenging. In this study, we produced the positron-emitting radionuclide ⁵²Mn (<i>t</i>_<i>1/2</i> = 5.6 d) by proton bombardment (<i>E</i>_<i>p</i><15 MeV) of chromium metal, followed by solid-phase isolation by cation-exchange chromatography. An aqueous solution of [⁵²Mn]MnCl₂ was nebulized into a closed chamber with openings through which mice inhaled the aerosol, and a separate cohort of mice received intravenous (IV) injections of [⁵²Mn]MnCl₂. <i>Ex vivo</i> biodistribution was performed at 1 h and 1 d post-injection/inhalation (p.i.). In both trials, we observed uptake in lungs and thyroid at 1 d p.i. Manganese is known to cross the blood-brain barrier, as confirmed in our studies following IV injection (0.86%ID/g, 1 d p.i.) and following inhalation of aerosol, (0.31%ID/g, 1 d p.i.). Uptake in salivary gland and pancreas were observed at 1 d p.i. (0.5 and 0.8%ID/g), but to a much greater degree from IV injection (6.8 and 10%ID/g). In a separate study, mice received IV injection of an imaging dose of [⁵²Mn]MnCl₂, followed by <i>in vivo</i> imaging by positron emission tomography (PET) and <i>ex vivo</i> biodistribution. The results from this study supported many of the results from the biodistribution-only studies. In this work, we have confirmed results in the literature and contributed new results for the biodistribution of inhaled radiomanganese for several organs. Our results could serve as supporting information for environmental and occupational regulations, for designing PET studies utilizing ⁵²Mn, and/or for predicting the biodistribution of manganese-based MR contrast agents.</p></div

The genomics of adaptation to climate in European great tit (Parus major) populations

The recognition that climate change is occurring at an unprecedented rate means that there is increased urgency in understanding how organisms can adapt to a changing environment. Wild great tit (Parus major) populations represent an attractive ecological model system to understand the genomics of climate adaptation. They are widely distributed across Eurasia and they have been documented to respond to climate change. We performed a Bayesian genome-environment analysis, by combining local climate data with single nucleotide polymorphisms genotype data from 20 European populations (broadly spanning the species’ continental range). We found 36 genes putatively linked to adaptation to climate. Following an enrichment analysis of biological process Gene Ontology (GO) terms, we identified over-represented terms and pathways among the candidate genes. Because many different genes and GO terms are associated with climate variables, it seems likely that climate adaptation is polygenic and genetically complex. Our findings also suggest that geographical climate adaptation has been occurring since great tits left their Southern European refugia at the end of the last ice age. Finally, we show that substantial climate-associated genetic variation remains, which will be essential for adaptation to future changes

First clinical experience of correcting phantom-based image distortion related to gantry position on a 0.35T MR-Linac

MR-guided radiotherapy requires strong imaging spatial integrity to deliver high quality plans and provide accurate dose calculation. The MRI system, however, can be compromised by the integrated linear accelerator (Linac), resulting in inaccurate imaging isocenter position and geometric distortion. Dependence on gantry position further complicates the correction of distortions. This work presents a new clinical application of a commercial phantom and software system that quantifies isocenter alignment and geometric distortion, as well as providing a deformation vector field (DVF). A large distortion phantom and a smaller grid phantom were imaged at multiple gantry angles from 0 to 330° on a 0.35 T integrated MR-Linac. The software package was used to assess geometric distortion and generate DVFs to correct distortions within the phantom volume. The DVFs were applied to the grid phantom with resampling software then evaluated using structural similarity index measure (SSIM). Scans were also performed with a ferromagnetic clip near the phantom to investigate the correction of more severe artifacts. The mean magnitude isocenter shift was 0.67 mm, ranging from 0.25 to 1.04 mm across all angles. The DVF had a mean component value of 0.27 ± 0.02, 0.24 ± 0.01, and 0.19 ± 0.01 mm in the right-left (RL), anterior-posterior (AP), and superior-inferior (SI) directions. The ferromagnetic clip increased isocenter position error from 1.98 mm to 2.20 mm and increased mean DVF component values in the RL and AP directions. The resampled grid phantom had an increased SSIM for all gantry angles compared to original images, increasing from 0.26 ± 0.001 to 0.70 ± 0.004. Through this clinical assessment, we were able to correct geometric distortion and isocenter shift related to gantry position on a 0.35 T MR-Linac using the distortion phantom and software package. This provides encouragement that it could be used for quality assurance and clinically to correct systematic distortion caused by imaging at different gantry angles

Direct grating writing: single-step Bragg grating and waveguide fabrication for telecommunications and sensing applications

Direct Grating Writing (DGW) has been developed over the past decade as a means of rapidly prototyping waveguides with integrated Bragg grating structures in silica-on-silicon substrates [1]. The technique allows complicated waveguide structures and Bragg grating arrays to be fabricated and characterised in house

Level of Pain and Disability at Time of TKR across the Past 10 Years: Results from Two National Cohorts

Introduction: A recent analysis reported a growing numbers of younger US adults with knee pain consistent with osteoarthritis (OA), although parallel analyses of knee x-rays found no increase in the classic radiographic signs of OA. The accompanying editorial evoked the need to understand if surgeons are performing surgery at an earlier stage in the condition.1 We compared pre-operative demographic and symptom profiles of a national US cohort of OA patients undergoing primary total knee replacement (TKR) in 2011-2012 with a national US cohort of patients from 2000-2004 to evaluate change, if any, in the timing of surgery as measured by patient pain and function. Methods: Following informed consent, the 2011-2012 national research study collected comprehensive data including demographic, comorbidity, and patient-reported pain and physical function, from a national sample of TKR patients. Comparable data from a national sample collected by one implant manufacturer between 2000-2004 were analyzed. Descriptive statistics compared the demographic and symptom profiles of the two cohorts. Results: There were fewer females in the 2011-2012 cohort (n=2363) compared to the 2000-2004 cohort (n=7144) (61.62%, vs. 66.72%). The 2011-2012 cohort was younger than the 2000-2004 cohort (66.7 years, vs. 68.12 years) and had a lower mean BMI (31.5 vs 32.3). Pre-operative physical function scores (SF36/PCS) were 3 points higher in 2011-2012 than 2000-2004 (33.2 vs. 30.41). When compared to the national PCS norm of 50 (SD=10), TKR patients from both time periods reported pre-operative function levels almost 2 standard deviations below the national norm. There was no significant difference in terms of emotional health (SF36/MCS scores: 51.85 for the 2011-2012 cohort vs. 51.83 for the 2000-2004 cohort). Conclusion: Despite the significant growth in the use of primary TKR in the last decade, especially among younger patients, TKR patients continue to report significant disability at the time of surgery

Assessment of a novel commercial large field of view phantom for comprehensive MR imaging quality assurance of a 0.35T MRgRT system

Consistent quality assurance (QA) programs are vital to MR-guided radiotherapy (MRgRT), for ensuring treatment is delivered accurately and the onboard MRI system is providing the expected image quality. However, daily imaging QA with a dedicated phantom is not common at many MRgRT centers, especially with large phantoms that cover a field of view (FOV), similar to the human torso. This work presents the first clinical experience with a purpose-built phantom for large FOV daily and periodic comprehensive quality assurance (QUASAR™ MRgRT Insight Phantom (beta)) from Modus Medical Devices Inc. (Modus QA) on an MRgRT system. A monthly American College of Radiology (ACR) QA phantom was also imaged for reference. Both phantoms were imaged on a 0.35T MR-Linac, a 1.5T Philips wide bore MRI, and a 3.0T Siemens MRI, with T1-weighted and T2-weighted acquisitions. The Insight phantom was imaged in axial and sagittal orientations. Image quality tests including geometric accuracy, spatial resolution accuracy, slice thickness accuracy, slice position accuracy, and image intensity uniformity were performed on each phantom, following their respective instruction manuals. The geometric distortion test showed similar distortions of -1.7 mm and -1.9 mm across a 190 mm and a 283 mm lengths for the ACR and MRgRT Insight phantoms, respectively. The MRgRT Insight phantom utilized a modulation transform function (MTF) for spatial resolution evaluation, which showed decreased performance on the lower

Characterization of radiotherapy component impact on MR imaging quality for an MRgRT system

Radiotherapy components of an magnetic resonnace-guided radiotherapy (MRgRT) system can alter the magnetic fields, causing spatial distortion and image deformation, altering imaging and radiation isocenter coincidence and the accuracy of dose calculations. This work presents a characterization of radiotherapy component impact on MR imaging quality in terms of imaging isocenter variation and spatial integrity changes on a 0.35T MRgRT system, pre- and postupgrade of the system. The impact of gantry position, MLC field size, and treatment table power state on imaging isocenter and spatial integrity were investigated. A spatial integrity phantom was used for all tests. Images were acquired for gantry angles 0-330° at 30° increments to assess the impact of gantry position. For MLC and table power state tests all images were acquired at the home gantry position (330°). MLC field sizes ranged from 1.66 to 27.4 cm edge length square fields. Imaging isocenter shift caused by gantry position was reduced from 1.7 mm at gantry 150° preupgrade to 0.9 mm at gantry 120° postupgrade. Maximum spatial integrity errors were 0.5 mm or less pre- and postupgrade for all gantry angles, MLC field sizes, and treatment table power states. However, when the treatment table was powered on, there was significant reduction in SNR. This study showed that gantry position can impact imaging isocenter, but spatial integrity errors were not dependent on gantry position, MLC field size, or treatment table power state. Significant isocenter variation, while reduced postupgrade, is cause for further investigation