Non-Binary and Binary Gender Identity in Australian Trans and Gender Diverse Individuals.

Many trans and gender diverse (TGD) people have gender identities that are not exclusively male or female but instead fall in-between or outside of the gender binary (non-binary). It remains unclear if and how those with non-binary gender identity differ from TGD individuals with binary identities. We aimed to understand the sociodemographic and mental health characteristics of people with non-binary identities compared with binary TGD identities. We performed a retrospective audit of new consultations for gender dysphoria between 2011 and 2016 in three clinical settings in Melbourne, Australia; (1) Equinox Clinic, an adult primary care clinic, (2) an adult endocrine specialist clinic, and (3) the Royal Children's Hospital, a child and adolescent specialist referral clinic. Age (grouped by decade), gender identity, sociodemographic, and mental health conditions were recorded. Of 895 TGD individuals, 128 (14.3%) had a non-binary gender. Proportions differed by clinical setting; 30.4% of people attending the adult primary care clinic, 7.4% attending the adult endocrine specialist clinic, and 8.0% attending the pediatric clinic identified as non-binary. A total of 29% of people in the 21-30-year-old age-group had a non-binary gender identity, higher than all other age-groups. Compared to TGD people with a binary gender identity, non-binary people had lower rates of gender-affirming interventions, and a higher prevalence of depression, anxiety, and illicit drug use. Tailoring clinical services to be inclusive of non-binary people and strategies to support mental health are required. Further research to better understand health needs and guide evidence-based gender-affirming interventions for non-binary people are needed.

Safety of Endovascular Thrombectomy for Acute Ischaemic Stroke in Anticoagulated Patients Ineligible for Intravenous Thrombolysis.

BACKGROUND/AIM: Endovascular thrombectomy may be performed in anticoagulated patients taking vitamin-K antagonists (VKA) or direct-acting oral anticoagulants (DOAC) in whom the use of intravenous tissue plasminogen activator (tPA) is contraindicated. We aimed to investigate the efficacy and safety of mechanical thrombectomy specifically in anticoagulated patients ineligible for thrombolysis. METHODS: We performed a retrospective analysis of a prospectively collected database of consecutive ischaemic stroke patients undergoing mechanical thrombectomy from January 2008 to June 2017. Patients receiving any dose of intravenous or intra-arterial thrombolysis were excluded. Patients taking oral anticoagulants (VKAs or DOACs) were compared with non-anticoagulated patients. Outcomes compared between groups included the rate of intracerebral haemorrhage (ICH) on follow-up imaging (ICHany), symptomatic ICH, functional independence at 90 days (modified Rankin scale score, 0-2), mortality, and post-treatment recanalization (Thrombolysis in Cerebral Infarction score ≥2b). RESULTS: In all, 102 patients undergoing mechanical thrombectomy without prior thrombolysis were included in the study. Sixty-six (64.7%) patients were not anticoagulated, 23 (22.5%) patients were taking VKAs, and 13 (12.7%) patients were taking DOACs. There were no significant differences in the rate of ICHany (11.1 vs. 13.6%, p = 0.93) or sICH (2.8 vs. 1.5%, p = 0.14) in anticoagulated patients compared to non-anticoagulated patients. No cases of sICH were observed among patients taking DOACs. After 90 days of follow-up, the rates of functional independence (50.0 vs. 43.1%) and mortality (27.8 vs. 25.8%) were also similar between the anticoagulation and the non-anticoagulation groups. CONCLUSION: Mechanical thrombectomy appears to be safe and effective in anticoagulated patients ineligible for thrombolysis, with observed haemorrhage rates similar to those of patients not on anticoagulant therapy. However, further multicentre prospective studies are needed, due to the rising number of patients on warfarin and DOACs worldwide.

Nitrile as Activating Group in the Asymmetric Bioreduction of ß-Cyanoacrylic Acids Catalyzed by Ene-Reductases.

Asymmetric bioreduction of an (E)-ß-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester.

Feasibility of Synchrotron-Based Ultra-High Dose Rate (UHDR) Proton Irradiation with Pencil Beam Scanning for FLASH Research.

BACKGROUND: This study aims to present the feasibility of developing a synchrotron-based proton ultra-high dose rate (UHDR) pencil beam scanning (PBS) system. METHODS: The RF extraction power in the synchrotron system was increased to generate 142.4 MeV pulsed proton beams for UHDR irradiation at ~100 nA beam current. The charge per spill was measured using a Faraday cup. The spill length and microscopic time structure of each spill was measured with a 2D strip transmission ion chamber. The measured UHDR beam fluence was used to derive the spot dwell time for pencil beam scanning. Absolute dose distributions at various depths and spot spacings were measured using Gafchromic films in a solid-water phantom. RESULTS: For proton UHDR beams at 142.4 MeV, the maximum charge per spill is 4.96 ± 0.10 nC with a maximum spill length of 50 ms. This translates to an average beam current of approximately 100 nA during each spill. Using a 2 × 2 spot delivery pattern, the delivered dose per spill at 5 cm and 13.5 cm depth is 36.3 Gy (726.3 Gy/s) and 56.2 Gy (1124.0 Gy/s), respectively. CONCLUSIONS: The synchrotron-based proton therapy system has the capability to deliver pulsed proton UHDR PBS beams. The maximum deliverable dose and field size per pulse are limited by the spill length and extraction charge.

Chemoenzymatic asymmetric synthesis of pregabalin precursors via asymmetric bioreduction of ß-cyanoacrylate esters using ene-reductases.

The asymmetric bioreduction of a library of ß-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications.

Characterization of a commercial bioluminescence tomography-guided system for pre-clinical radiation research.

BACKGROUND: Widely used Cone-beam computed tomography (CBCT)-guided irradiators have limitations in localizing soft tissue targets growing in a low-contrast environment. This hinders small animal irradiators achieving precise focal irradiation. PURPOSE: To advance image-guidance for soft tissue targeting, we developed a commercial-grade bioluminescence tomography-guided system (BLT, MuriGlo) for pre-clinical radiation research. We characterized the system performance and demonstrated its capability in target localization. We expect this study can provide a comprehensive guideline for the community in utilizing the BLT system for radiation studies. METHODS: MuriGlo consists of four mirrors, filters, lens, and charge-coupled device (CCD) camera, enabling a compact imaging platform and multi-projection and multi-spectral BLT. A newly developed mouse bed allows animals imaged in MuriGlo and transferred to a small animal radiation research platform (SARRP) for CBCT imaging and BLT-guided irradiation. Methods and tools were developed to evaluate the CCD response linearity, minimal detectable signal, focusing, spatial resolution, distortion, and uniformity. A transparent polycarbonate plate covering the middle of the mouse bed was used to support and image animals from underneath the bed. We investigated its effect on 2D Bioluminescence images and 3D BLT reconstruction accuracy, and studied its dosimetric impact along with the rest of mouse bed. A method based on pinhole camera model was developed to map multi-projection bioluminescence images to the object surface generated from CBCT image. The mapped bioluminescence images were used as the input data for the optical reconstruction. To account for free space light propagation from object surface to optical detector, a spectral derivative (SD) method was implemented for BLT reconstruction. We assessed the use of the SD data (ratio imaging of adjacent wavelength) in mitigating out of focusing and non-uniformity seen in the images. A mouse phantom was used to validate the data mapping. The phantom and an in vivo glioblastoma model were utilized to demonstrate the accuracy of the BLT target localization. RESULTS: The CCD response shows good linearity with < 0.6% residual from a linear fit. The minimal detectable level is 972 counts for 10 × 10 binning. The focal plane position is within the range of 13-18 mm above the mouse bed. The spatial resolution of 2D optical imaging is < 0.3 mm at Rayleigh criterion. Within the region of interest, the image uniformity is within 5% variation, and image shift due to distortion is within 0.3 mm. The transparent plate caused < 6% light attenuation. The use of the SD imaging data can effectively mitigate out of focusing, image non-uniformity, and the plate attenuation, to support accurate multi-spectral BLT reconstruction. There is < 0.5% attenuation on dose delivery caused by the bed. The accuracy of data mapping from the 2D bioluminescence images to CBCT image is within 0.7 mm. Our phantom test shows the BLT system can localize a bioluminescent target within 1 mm with an optimal threshold and only 0.2 mm deviation was observed for the case with and without a transparent plate. The same localization accuracy can be maintained for the in vivo GBM model. CONCLUSIONS: This work is the first systematic study in characterizing the commercial BLT-guided system. The information and methods developed will be useful for the community to utilize the imaging system for image-guided radiation research.

FLASH Effects Induced by Orthovoltage X-Rays.

PURPOSE: This work describes the first implementation and in vivo study of ultrahigh-dose-rate radiation (>37 Gy/s; FLASH) effects induced by kilovoltage (kV) x-ray from a rotating-anode x-ray source. METHODS AND MATERIALS: A high-capacity rotating-anode x-ray tube with an 80-kW generator was implemented for preclinical FLASH radiation research. A custom 3-dimensionally printed immobilization and positioning tool was developed for reproducible irradiation of a mouse hind limb. Calibrated Gafchromic (EBT3) film and thermoluminescent dosimeters (LiF:Mg,Ti) were used for in-phantom and in vivo dosimetry. Healthy FVB/N and FVBN/C57BL/6 outbred mice were irradiated on 1 hind leg to doses up to 43 Gy at FLASH (87 Gy/s) and conventional (CONV; <0.05 Gy/s) dose rates. The radiation doses were delivered using a single pulse with the widths up to 500 ms and 15 minutes at FLASH and CONV dose rates. Histologic assessment of radiation-induced skin damage was performed at 8 weeks posttreatment. Tumor growth suppression was assessed using a B16F10 flank tumor model in C57BL6J mice irradiated to 35 Gy at both FLASH and CONV dose rates. RESULTS: FLASH-irradiated mice experienced milder radiation-induced skin injuries than CONV-irradiated mice, visible by 4 weeks posttreatment. At 8 weeks posttreatment, normal tissue injury was significantly reduced in FLASH-irradiated animals compared with CONV-irradiated animals for histologic endpoints including inflammation, ulceration, hyperplasia, and fibrosis. No difference in tumor growth response was observed between FLASH and CONV irradiations at 35 Gy. The normal tissue sparing effects of FLASH irradiations were observed only for high-severity endpoint of ulceration at 43 Gy, which suggests the dependency of biologic endpoints to FLASH radiation dose. CONCLUSIONS: Rotating-anode x-ray sources can achieve FLASH dose rates in a single pulse with dosimetric properties suitable for small-animal experiments. We observed FLASH normal tissue sparing of radiation toxicities in mouse skin irradiated at 35 Gy with no sacrifice to tumor growth suppression. This study highlights an accessible new modality for laboratory study of the FLASH effect.

A role for the TGFbeta-Par6 polarity pathway in breast cancer progression.

The role of polarity signaling in cancer metastasis is ill defined. Using two three-dimensional culture models of mammary epithelial cells and an orthotopic mouse model of breast cancer, we reveal that Par6 signaling, which is regulated directly by TGFbeta, plays a role in breast cancer metastasis. Interference with Par6 signaling blocked TGFbeta-dependent loss of polarity in acini-like structures formed by non-transformed mammary cells grown in three-dimensional structures and suppressed the protrusive morphology of mesenchymal-like invasive mammary tumor cells without rescuing E-cadherin expression. Moreover, blockade of Par6 signaling in an in vivo orthotopic model of metastatic breast cancer induced the formation of ZO-1-positive epithelium-like structures in the primary tumor and suppressed metastasis to the lungs. Analysis of the pathway in tissue microarrays of human breast tumors further revealed that Par6 activation correlated with markers of the basal carcinoma subtype in BRCA1-associated tumors. These studies thus reveal a key role for polarity signaling and the control of morphologic transformation in breast cancer metastasis.

Bioluminescence tomography system for in vivo irradiation guidance.

We constructed a bioluminescence tomography(BLT) to localize soft tissue targets for preclinical radiotherapy study. With the threshold and margin designed for target volume, BLT can provide opportunity to perform conformal irradiation to malignancy.

Quantitative Bioluminescence Tomography for In Vivo Volumetric-Guided Radiotherapy.

Several groups, including ours, have initiated efforts to develop small-animal irradiators that mimic radiation therapy (RT) for human treatment. The major image modality used to guide irradiation is cone-beam computed tomography (CBCT). While CBCT provides excellent guidance capability, it is less adept at localizing soft tissue targets growing in a low image contrast environment. In contrast, bioluminescence imaging (BLI) provides strong image contrast and thus is an attractive solution for soft tissue targeting. However, commonly used 2D BLI on an animal surface is inadequate to guide irradiation, because optical transport from an internal bioluminescent tumor is highly susceptible to the effects of optical path length and tissue absorption and scattering. Recognition of these limitations led us to integrate 3D bioluminescence tomography (BLT) with the small animal radiation research platform (SARRP). In this chapter, we introduce quantitative BLT (QBLT) with the advanced capabilities of quantifying tumor volume for irradiation guidance. The detail of system components, calibration protocol, and step-by-step procedure to conduct the QBLT-guided irradiation are described.

Mobile bioluminescence tomography-guided system for pre-clinical radiotherapy research.

Due to low imaging contrast, a widely-used cone-beam computed tomography-guided small animal irradiator is less adept at localizing in vivo soft tissue targets. Bioluminescence tomography (BLT), which combines a model of light propagation through tissue with an optimization algorithm, can recover a spatially resolved tomographic volume for an internal bioluminescent source. We built a novel mobile BLT system for a small animal irradiator to localize soft tissue targets for radiation guidance. In this study, we elaborate its configuration and features that are indispensable for accurate image guidance. Phantom and in vivo validations show the BLT system can localize targets with accuracy within 1 mm. With the optimal choice of threshold and margin for target volume, BLT can provide a distinctive opportunity for investigators to perform conformal biology-guided irradiation to malignancy.

Improvement in DCIS detection rates by MRI over time in a high-risk breast screening study.

Although magnetic resonance imaging (MRI) is much more sensitive than mammography for detecting early invasive breast cancer, in many high-risk screening studies MRI was less sensitive than mammography for detecting ductal carcinoma in situ (DCIS). We reviewed our experience detecting DCIS in our single center study of annual MRI, mammography, ultrasound and clinical breast examination (CBE) for screening very high-risk women. All cases of DCIS±microinvasion and invasive cancer were compared in two time frames: before (period A) and after (period B) July 2001-when we acquired expertise in the detection of DCIS with MRI-with respect to patient demographics, method of detection, and rates of detection of invasive cancer and DCIS. In period A there were 15 cases (3.1% of 486 screens) in 223 women, of which 2 (13%) were DCIS-one with microinvasion-neither detected by MRI. In period B there were 29 cases (3.3% of 877 screens) in 391 women, of which 10 (34%) were DCIS±microinvasion (p=0.04), all 10 detected by MRI but only one by mammography. No DCIS cases were detected by ultrasound or CBE. Specificity was lower in period B than in period A but acceptable. The ability to detect DCIS with screening MRI improves significantly with experience. MRI-guided biopsy capability is essential for a high-risk screening program. In experienced centers the increased sensitivity of MRI relative to mammography is at least as high for DCIS as it is for invasive breast cancer.

Ultrahigh dose-rate (FLASH) x-ray irradiator for pre-clinical laboratory research.

FLASH irradiation has been shown to reduce significantly normal tissue toxicity compared to conventional irradiation, while maintaining tumor control probability at similar level. Clinical translation of FLASH irradiation necessitates comprehensive laboratory studies to elucidate biological effects as well as pertinent technological and physical requirements. At present, FLASH research employs complex accelerator technologies of limited accessibilities. Here, we study the feasibility of a novel self-shielded x-ray irradiation cabinet system, as an enabling technology to enhance the preclinical research capabilities. The proposed system employs two commercially available high capacity 150 kVp fluoroscopy x-ray sources with rotating anode technology in a parallel-opposed arrangement. Simulation was performed with the GEANT4 Monte-Carlo platform. Simulated dosimetric properties of the x-ray beam for both FLASH and conventional dose-rate irradiations were characterized. Dose and dose rate from a single kV x-ray fluoroscopy source in solid water phantom were verified with measurements using Gafchromic films. The parallel-opposed x-ray sources can deliver over 50 Gy doses to a 20 mm thick water equivalent medium at ultrahigh dose-rates of 40-240 Gy s-1. A uniform depth-dose rate (±5%) is achieved over 8-12 mm in the central region of the phantom. Mirrored beams minimize heel effect of the source and achieve reasonable cross-beam uniformity (±3%). Conventional dose-rate irradiation (≤0.1 Gy s-1) can also be achieved by reducing the tube current and increasing the distance between the phantom and tubes. The rotating anode x-ray source can be used to deliver both FLASH and conventional dose-rate irradiations with the field dimensions well suitable for small animal and cell-culture irradiations. For FLASH irradiation using parallel-opposed sources, entrance and exit doses can be higher by 30% than the dose at the phantom center. Beam angling can be employed to minimize the high surface doses. Our proposed system is amendable to self-shielding and enhance research in regular laboratory setting.

Quantitative Bioluminescence Tomography-Guided Conformal Irradiation for Preclinical Radiation Research.

PURPOSE: Widely used cone beam computed tomography (CBCT)-guided irradiators in preclinical radiation research are limited to localize soft tissue target because of low imaging contrast. Knowledge of target volume is a fundamental need for radiation therapy (RT). Without such information to guide radiation, normal tissue can be overirradiated, introducing experimental uncertainties. This led us to develop high-contrast quantitative bioluminescence tomography (QBLT) for guidance. The use of a 3-dimensional bioluminescence signal, related to cell viability, for preclinical radiation research is one step toward biology-guided RT. METHODS AND MATERIALS: Our QBLT system enables multiprojection and multispectral bioluminescence imaging to maximize input data for the tomographic reconstruction. Accurate quantification of spectrum and dynamic change of in vivo signal were also accounted for the QBLT. A spectral-derivative method was implemented to eliminate the modeling of the light propagation from animal surface to detector. We demonstrated the QBLT capability of guiding conformal RT using a bioluminescent glioblastoma (GBM) model in vivo. A threshold was determined to delineate QBLT reconstructed gross target volume (GTVQBLT), which provides the best overlap between the GTVQBLT and CBCT contrast labeled GBM (GTV), used as the ground truth for GBM volume. To account for the uncertainty of GTVQBLT in target positioning and volume delineation, a margin was determined and added to the GTVQBLT to form a QBLT planning target volume (PTVQBLT) for guidance. RESULTS: The QBLT can reconstruct in vivo GBM with localization accuracy within 1 mm. A 0.5-mm margin was determined and added to GTVQBLT to form PTVQBLT, largely improving tumor coverage from 75.0% (0 mm margin) to 97.9% in average, while minimizing normal tissue toxicity. With the goal of prescribed dose 5 Gy covering 95% of PTVQBLT, QBLT-guided 7-field conformal RT can effectively irradiate 99.4 ± 1.0% of GTV. CONCLUSIONS: The QBLT provides a unique opportunity for investigators to use biologic information for target delineation, guiding conformal irradiation, and reducing normal tissue involvement, which is expected to increase reproducibility of scientific discovery.

Development of a Mobile Fluorescence Tomography-guided System for Pre-clinical Radiotherapy Research.

We proposed to build a mobile fluorescence tomography (mFT) system as an image-guided platform for pre-clinical radiotherapy research. The mFT system is expected to localize functional target/tumor, guide irradiation, and provide longitudinal treatment assessment.

In vivo bioluminescence tomography-guided radiation research platform for pancreatic cancer: an initial study using subcutaneous and orthotopic pancreatic tumor models.

Genetically engineered mouse model(GEMM) that develops pancreatic ductal adenocarcinoma(PDAC) offers an experimental system to advance our understanding of radiotherapy(RT) for pancreatic cancer. Cone beam CT(CBCT)-guided small animal radiation research platform(SARRP) has been developed to mimic the RT used for human. However, we recognized that CBCT is inadequate to localize the PDAC growing in low image contrast environment. We innovated bioluminescence tomography(BLT) to guide SARRP irradiation for in vivo PDAC. Before working on the complex PDAC-GEMM, we first validated our BLT target localization using subcutaneous and orthotopic pancreatic tumor models. Our BLT process involves the animal transport between the BLT system and SARRP. We inserted a titanium wire into the orthotopic tumor as the fiducial marker to track the tumor location and to validate the BLT reconstruction accuracy. Our data shows that with careful animal handling, minimum disturbance for target position was introduced during our BLT imaging procedure(<0.5mm). However, from longitudinal 2D bioluminescence image(BLI) study, the day-to-day location variation for an abdominal tumor can be significant. We also showed that the 2D BLI in single projection setting cannot accurately capture the abdominal tumor location. It renders that 3D BLT with multiple-projection is needed to quantify the tumor volume and location for precise radiation research. Our initial results show the BLT can retrieve the location at 2mm accuracy for both tumor models, and the tumor volume can be delineated within 25% accuracy. The study for the subcutaneous and orthotopic models will provide us valuable knowledge for BLT-guided PDAC-GEMM radiation research.

In Vivo Bioluminescence Tomography Center of Mass-Guided Conformal Irradiation.

PURPOSE: The cone-beam computed tomography (CBCT)-guided small animal radiation research platform (SARRP) has provided unique opportunities to test radiobiologic hypotheses. However, CBCT is less adept to localize soft tissue targets growing in a low imaging contrast environment. Three-dimensional bioluminescence tomography (BLT) provides strong image contrast and thus offers an attractive solution. We introduced a novel and efficient BLT-guided conformal radiation therapy and demonstrated it in an orthotopic glioblastoma (GBM) model. METHODS AND MATERIALS: A multispectral BLT system was integrated with SARRP for radiation therapy (RT) guidance. GBM growth curve was first established by contrast CBCT/magnetic resonance imaging (MRI) to derive equivalent sphere as approximated gross target volume (aGTV). For BLT, mice were subject to multispectral bioluminescence imaging, followed by SARRP CBCT imaging and optical reconstruction. The CBCT image was acquired to generate anatomic mesh for the reconstruction and RT planning. To ensure high accuracy of the BLT-reconstructed center of mass (CoM) for target localization, we optimized the optical absorption coefficients µa by minimizing the distance between the CoMs of BLT reconstruction and contrast CBCT/MRI-delineated GBM volume. The aGTV combined with the uncertainties of BLT CoM localization and target volume determination was used to generate estimated target volume (ETV). For conformal irradiation procedure, the GBM was first localized by the predetermined ETV centered at BLT-reconstructed CoM, followed by SARRP radiation. The irradiation accuracy was qualitatively confirmed by pathologic staining. RESULTS: Deviation between CoMs of BLT reconstruction and contrast CBCT/MRI-imaged GBM is approximately 1 mm. Our derived ETV centered at BLT-reconstructed CoM covers >95% of the tumor volume. Using the second-week GBM as an example, the ETV-based BLT-guided irradiation can cover 95.4% ± 4.7% tumor volume at prescribed dose. The pathologic staining demonstrated the BLT-guided irradiated area overlapped well with the GBM location. CONCLUSIONS: The BLT-guided RT enables 3-dimensional conformal radiation for important orthotopic tumor models, which provides investigators a new preclinical research capability.

2D ultrasound imaging based intra-fraction respiratory motion tracking for abdominal radiation therapy using machine learning.

We have previously developed a robotic ultrasound imaging system for motion monitoring in abdominal radiation therapy. Owing to the slow speed of ultrasound image processing, our previous system could only track abdominal motions under breath-hold. To overcome this limitation, a novel 2D-based image processing method for tracking intra-fraction respiratory motion is proposed. Fifty-seven different anatomical features acquired from 27 sets of 2D ultrasound sequences were used in this study. Three 2D ultrasound sequences were acquired with the robotic ultrasound system from three healthy volunteers. The remaining datasets were provided by the 2015 MICCAI Challenge on Liver Ultrasound Tracking. All datasets were preprocessed to extract the feature point, and a patient-specific motion pattern was extracted by principal component analysis and slow feature analysis (SFA). The tracking finds the most similar frame (or indexed frame) by a k-dimensional-tree-based nearest neighbor search for estimating the tracked object location. A template image was updated dynamically through the indexed frame to perform a fast template matching (TM) within a learned smaller search region on the incoming frame. The mean tracking error between manually annotated landmarks and the location extracted from the indexed training frame is 1.80 ± 1.42 mm. Adding a fast TM procedure within a small search region reduces the mean tracking error to 1.14 ± 1.16 mm. The tracking time per frame is 15 ms, which is well below the frame acquisition time. Furthermore, the anatomical reproducibility was measured by analyzing the location's anatomical landmark relative to the probe; the position-controlled probe has better reproducibility and yields a smaller mean error across all three volunteer cases, compared to the force-controlled probe (2.69 versus 11.20 mm in the superior-inferior direction and 1.19 versus 8.21 mm in the anterior-posterior direction). Our method reduces the processing time for tracking respiratory motion significantly, which can reduce the delivery uncertainty.

Evaluation of classification and regression tree (CART) model in weight loss prediction following head and neck cancer radiation therapy.

OBJECTIVE: We explore whether a knowledge-discovery approach building a Classification and Regression Tree (CART) prediction model for weight loss (WL) in head and neck cancer (HNC) patients treated with radiation therapy (RT) is feasible. METHODS AND MATERIALS: HNC patients from 2007 to 2015 were identified from a prospectively collected database Oncospace. Two prediction models at different time points were developed to predict weight loss ≥5 kg at 3 months post-RT by CART algorithm: (1) during RT planning using patient demographic, delineated dose data, planning target volume-organs at risk shape relationships data and (2) at the end of treatment (EOT) using additional on-treatment toxicities and quality of life data. RESULTS: Among 391 patients identified, WL predictors during RT planning were International Classification of Diseases diagnosis; dose to masticatory and superior constrictor muscles, larynx, and parotid; and age. At EOT, patient-reported oral intake, diagnosis, N stage, nausea, pain, dose to larynx, parotid, and low-dose planning target volume-larynx distance were significant predictive factors. The area under the curve during RT and EOT was 0.773 and 0.821, respectively. CONCLUSIONS: We demonstrate the feasibility and potential value of an informatics infrastructure that has facilitated insight into the prediction of WL using the CART algorithm. The prediction accuracy significantly improved with the inclusion of additional treatment-related data and has the potential to be leveraged as a strategy to develop a learning health system.

Breast cancers detected with imaging screening in the BRCA population: emphasis on MR imaging with histopathologic correlation.

The benefit of screening with breast magnetic resonance (MR) imaging for certain patient populations at high risk for breast cancer, most notably patients with a genetic mutation in the BRCA1 or BRCA2 gene, has been established in numerous studies and is now becoming part of routine clinical practice. Despite the lower sensitivity of mammography compared with that of MR imaging, the former remains the standard of care for screening any patient population. In the BRCA1 and BRCA2 populations, the inferior sensitivity and specificity of ultrasonography (US) limit its role as a screening tool, but US remains a vital diagnostic tool because of its ability to provide guidance for biopsy of many suspicious lesions detected with MR imaging. Important features of a screening program with breast MR imaging include the following: optimization of the MR imaging technique, an awareness of the imaging features of invasive and noninvasive breast cancers detected with MR imaging, an understanding of the limitations of the various imaging modalities in both the initial screening and subsequent diagnostic work-up evaluations, and the requirement for MR imaging-guided biopsy.