Radiomics for Response and Outcome Assessment for Non-Small Cell Lung Cancer.

Routine follow-up visits and radiographic imaging are required for outcome evaluation and tumor recurrence monitoring. Yet more personalized surveillance is required in order to sufficiently address the nature of heterogeneity in nonsmall cell lung cancer and possible recurrences upon completion of treatment. Radiomics, an emerging noninvasive technology using medical imaging analysis and data mining methodology, has been adopted to the area of cancer diagnostics in recent years. Its potential application in response assessment for cancer treatment has also drawn considerable attention. Radiomics seeks to extract a large amount of valuable information from patients' medical images (both pretreatment and follow-up images) and quantitatively correlate image features with diagnostic and therapeutic outcomes. Radiomics relies on computers to identify and analyze vast amounts of quantitative image features that were previously overlooked, unmanageable, or failed to be identified (and recorded) by human eyes. The research area has been focusing on the predictive accuracy of pretreatment features for outcome and response and the early discovery of signs of tumor response, recurrence, distant metastasis, radiation-induced lung injury, death, and other outcomes, respectively. This review summarized the application of radiomics in response assessments in radiotherapy and chemotherapy for non-small cell lung cancer, including image acquisition/reconstruction, region of interest definition/segmentation, feature extraction, and feature selection and classification. The literature search for references of this article includes PubMed peer-reviewed publications over the last 10 years on the topics of radiomics, textural features, radiotherapy, chemotherapy, lung cancer, and response assessment. Summary tables of radiomics in response assessment and treatment outcome prediction in radiation oncology have been developed based on the comprehensive review of the literature

Towards Quantitative Endoscopy with Vision Intelligence

In this thesis, we work on topics related to quantitative endoscopy with vision-based intelligence. Specifically, our works revolve around the topic of video reconstruction in endoscopy, where many challenges exist, such as texture scarceness, illumination variation, multimodality, etc., and these prevent prior works from working effectively and robustly. To this end, we propose to combine the strength of expressivity of deep learning approaches and the rigorousness and accuracy of non-linear optimization algorithms to develop a series of methods to confront such challenges towards quantitative endoscopy. We first propose a retrospective sparse reconstruction method that can estimate a high-accuracy and density point cloud and high-completeness camera trajectory from a monocular endoscopic video with state-of-the-art performance. To enable this, replacing the role of a hand-crafted local descriptor, a deep image feature descriptor is developed to boost the feature matching performance in a typical sparse reconstruction algorithm. A retrospective surface reconstruction pipeline is then proposed to estimate a textured surface model from a monocular endoscopic video, where self-supervised depth and descriptor learning and surface fusion technique is involved. We show that the proposed method performs superior to a popular dense reconstruction method and the estimate reconstructions are in good agreement with the surface models obtained from CT scans. To align video-reconstructed surface models with pre-operative imaging such as CT, we introduce a global point cloud registration algorithm that is robust to resolution mismatch that often happens in such multi-modal scenarios. Specifically, a geometric feature descriptor is developed where a novel network normalization technique is used to help a 3D network produce more consistent and distinctive geometric features for samples with different resolutions. The proposed geometric descriptor achieves state-of-the-art performance, based on our evaluation. Last but not least, a real-time SLAM system that estimates a surface geometry and camera trajectory from a monocular endoscopic video is developed, where deep representations for geometry and appearance and non-linear factor graph optimization are used. We show that the proposed SLAM system performs favorably compared with a state-of-the-art feature-based SLAM system

2012 Activity Report of the Regional Research Programme on Hadrontherapy for the ETOILE Center

2012 is the penultimate year of financial support by the CPER 2007-2013 for ETOILE's research program, sustained by the PRRH at the University Claude Bernard. As with each edition we make the annual review of the research in this group, so active for over 12 years now. Over the difficulties in the decision-making process for the implementation of the ETOILE Center, towards which all our efforts are focussed, some "themes" (work packages) were strengthened, others have progressed, or have been dropped. This is the case of the eighth theme (technological developments), centered around the technology for rotative beam distribution heads (gantries) and, after being synchronized with the developments of ULICE's WP6, remained so by ceasing its activities, coinciding also with the retirement of its historic leader at IPNL, Marcel Bajard. Topic number 5 ("In silico simulations") has suffered the departure of its leader, Benjamin Ribba, although the work has still been provided by Branka Bernard, a former postdoctoral fellow in Lyon Sud, and now back home in Croatia, still in contract with UCBL for the ULICE project. Aside from these two issues (and the fact that the theme "Medico-economical simulations" is now directly linked to the first one ("Medical Project"), the rest of the teams are growing, as evidenced by the publication statistics at the beginning of this report. This is obviously due to the financial support of our always faithful regional institutions, but also to the synergy that the previous years, the European projects, the arrival of the PRIMES LabEx, and the national France Hadron infrastructure have managed to impulse. The Rhone-Alpes hadron team, which naturally includes the researchers of LPC at Clermont, should also see its influence result in a strong presence in France Hadron's regional node, which is being organized. The future of this regional research is not yet fully guaranteed, especially in the still uncertain context of ETOILE, but the tracks are beginning to emerge to allow past and present efforts translate into a long future that we all want to see established. Each of the researchers in PRRH is aware that 2013 will be (and already is) the year of great challenge : for ETOILE, for the PRRH, for hadron therapy in France, for French hadrontherapy in Europe (after the opening and beginning of treatments in the German [HIT Heidelberg, Marburg], Italian [CNAO, Pavia] and Austrian [MedAustron, Wien Neuerstadt]) centers. Let us meet again in early 2014 for a comprehensive review of the past and a perspective for the future ..

Modeling Humans at Rest with Applications to Robot Assistance

Humans spend a large part of their lives resting. Machine perception of this class of body poses would be beneficial to numerous applications, but it is complicated by line-of-sight occlusion from bedding. Pressure sensing mats are a promising alternative, but data is challenging to collect at scale. To overcome this, we use modern physics engines to simulate bodies resting on a soft bed with a pressure sensing mat. This method can efficiently generate data at scale for training deep neural networks. We present a deep model trained on this data that infers 3D human pose and body shape from a pressure image, and show that it transfers well to real world data. We also present a model that infers pose, shape and contact pressure from a depth image facing the person in bed, and it does so in the presence of blankets. This model similarly benefits from synthetic data, which is created by simulating blankets on the bodies in bed. We evaluate this model on real world data and compare it to an existing method that requires RGB, depth, thermal and pressure imagery in the input. Our model only requires an input depth image, yet it is 12% more accurate. Our methods are relevant to applications in healthcare, including patient acuity monitoring and pressure injury prevention. We demonstrate this work in the context of robotic caregiving assistance, by using it to control a robot to move to locations on a person’s body in bed.Ph.D

Characterization of resistance to Fusarium head blight in bread and durum wheat

Fusarium head blight (FHB) caused primarily by Fusarium graminearum (Fg) Schwabe (telomorph: Gibberella zeae Schw. [Petch]) in North America, is one of the most devstating diseases of wheat in Canada. An integrated approach to manage this disease is recommended that combines the adoption of cultural practices (tillage and crop rotation), cultivar resistance, and fungicide application at recommended timings. Resistance to FHB in wheat is a quantitatively inherited trait and highly influenced by environmental conditions. Sources of resistance are available in common wheat but not for durum wheat. There are no commercially available durum cultivars which are moderately resistant in North America which in part, can be explained by a lack of resistance in the primary gene pool. The current study was designed to study the effects (on disease suppression and linkage-drag associated with introgressions) of Sumai 3 derived Fhb1, Fhb2, and Fhb5 genes in hard red spring wheat cultivars [near-isogenic lines (NILs) developed in CDC Go and CDC Alsask backgrounds] from western Canada, the interaction of Fhb1 and Fhb5 with metconazole fungicide, and the mapping of quantitative trait loci (QTL) from emmer and durum wheat lines. The last part of the study utilized X-ray computed tomography as a tool to image selected NILs in the CDC Alsask background and focused on identification of key tissues conferring Type-II resistance to Fg. The phenotypic response of NILs carrying combinations of Sumai 3-derived genes suggested non-additive responses and Fhb5 was as effective as Fhb1 in conferring field resistance in both populations. Four to five resistance improving alleles, other than Fhb1, Fhb2, and Fhb5, in both populations were identified and three of five in the CDC Go population were contributed by the susceptible parent. The regions carrying these resistance improving alleles encoded disease resistance proteins, protein kinases, nucleotide-binding and leucine rich repeats’ domains. Complex epistatic gene-gene interactions among marker loci (including Fhb1, Fhb2, Fhb5) explained >20% of the phenotypic variation in FHB infection measurements. For the linkage drag experiment, introgressions resulted in lower thousand kernel weight and increased plant height with Fhb5. Among end-use quality traits, SDS-sedimentation volume and grain protein content were affected. In addition to Fhb1, Fhb2, Fhb5, we identified 10 loci in CDC Alsask NILs and nine in CDC Go NILs that affected the traits measured and none of these additional loci were common in both populations indicating the presence of multiple alleles in exotic sources that can result in linkage drag. Linkage drag is largely dependent on genetic background and the proportion of donor resistance alleles, thus, we observed more adverse effects among CDC Alsask NILs than among CDC Go NILs. Improvements in FHB resistance can still be made by introgressing the major genes examined in this study by using marker-assisted selection and selecting rare segregants with improved agronomy and end-use quality. There was an additive effect of Sumai 3-derived genes with metconazole in suppressing FHB and deoxynivalenol (DON) accumulation in the grain. Despite higher fungicide efficacy on moderately susceptible (MS) genotypes, FHB severity was greater on MS as compared to moderately resistant (MR) genotypes. Application of fungicides is warranted even on MR cultivars under moderate and high FHB disease pressure to reduce the amount of Fusarium damaged kernels (FDKs) and DON accumulation. In the QTL mapping study of tetraploid wheat, fifteen QTL (derived from both parents) for FHB resistance were identified on 11 of the 14 chromosomes using saturated linkage maps and a majority of the QTL were consistently detected in multiple environments. The combination of four relative large-effect and promising QTL reduced field FHB index, severity, incidence and visual rating index by 59%, 48%, 30%, and 29%, respectively. The majority of the QTL reported in the current study are novel and represent narrow intervals between the flanking markers; therefore, marker-assisted selection shoulb be of value in breeding FHB resistant durum wheat cultivars. In the final study of this thesis, as a proof-of-concept, we showcased the successful use of synchrotron-based X-ray imaging techniques to study the wheat-Fg interaction. This work indicated/re-confirmed the structural role of rachilla and rachis nodes in Type-II resistance to Fg in wheat. The results from all these studies will help wheat breeders to make decisions on introgressing exotic FHB resistance genes into common wheat. Additionally, novel QTL identified in tetraploid wheat can be used to enhance resistance in elite durum wheat lines by marker-assisted selection

Quantitative PET and SPECT

Since the introduction of personalized medicine, the primary focus of imaging has moved from detection and diagnosis to tissue characterization, the determination of prognosis, prediction of treatment efficacy, and measurement of treatment response. Precision (personalized) imaging heavily relies on the use of hybrid technologies and quantitative imaging biomarkers. The growing number of promising theragnostics require accurate quantification for pre- and post-treatment dosimetry. Furthermore, quantification is required in the pharmacokinetic analysis of new tracers and drugs and in the assessment of drug resistance. Positron Emission Tomography (PET) is, by nature, a quantitative imaging tool, relating the time–activity concentration in tissues and the basic functional parameters governing the biological processes being studied. Recent innovations in single photon emission computed tomography (SPECT) reconstruction techniques have allowed for SPECT to move from relative/semi-quantitative measures to absolute quantification. The strength of PET and SPECT is that they permit whole-body molecular imaging in a noninvasive way, evaluating multiple disease sites. Furthermore, serial scanning can be performed, allowing for the measurement of functional changes over time during therapeutic interventions. This Special Issue highlights the hot topics on quantitative PET and SPECT

Outcomes of MR-guided Stereotactic Body Radiotherapy (SBRT) or yttrium-90 Transarterial Radioembolization for Hepatocellular Carcinoma Treated at an Urban Liver Transplant Center

Background: There are overlapping indications for both stereotactic body radiotherapy (SBRT) and yttrium-90 (Y90) trans-arterial radioembolization as locoregional treatments for hepatocellular cancer, though most centers preferentially use one modality over the other. MR-guided radiation allows both effective on-table localization and integrated motion management as compared with many traditional linear accelerators, allowing SBRT to be done more easily. Y90 radioembolization has been a well-established modality to deliver highly conformal dose due to the localization of the microspheres to the vascular supply of a tumor. We looked at patient characteristics and treatment outcomes for patients receiving MR-guided SBRT or Y90 at an urban transplant center. Objectives: To compare patient characteristics and treatment outcomes of MR-guided SBRT with Y90 transarterial radioembolization in a liver transplant center. Methods: This retrospective single-institution study analyzed patients with HCC treated with SBRT or Y90 from August 2017 to September 2020. To select a patient population eligible for either treatment modality, any Y90 procedures for lesions \u3e 10 cm or for treatment volumes \u3e 1000 cc were omitted from the cohort. A total of 239 patients were included in the analysis, receiving a total of 98 courses of SBRT and 187 courses of Y90 treatment. Local control (LC), freedom from liver progression (FFLP), and overall survival (OS) rates were measured from treatment completion date to death date or last follow-up. All outcomes were censored at time of loss to follow-up; LC and FFLP were censored at time of liver transplant if applicable. Cox regression models were used for survival, with significant factors on the univariate analysis further analyzed with a multivariate model. Results: Median time to follow-up was 11 months (0-44 mo). The mean size of lesions treated with SBRT were smaller than those treated with Y90 (2.7 cm vs 4.3 cm, P\u3c0.01). The groups of patients differed in liver disease characteristics, with SBRT patients having fewer Child-Pugh A disease (62% vs 80%, P\u3c0.01), more having received locoregional treatments to the liver in the past (81% v 35%, P\u3c0.01), and more disease in previously treated liver (57% vs 25%, P\u3c0.01). Dose of radiation for SBRT was 45-50 Gy administered in 5 fractions; dose of Y90 radiation to tumor was prescribed to a median of 235.2 Gy (range 55.8-512.3 Gy). There was a higher rate of one year LC in the SBRT cohort (77% vs 57%, P\u3c0.01), while median FFLP (9 mo vs 8 mo, P=NS) and median OS were not significantly different (24 mo vs 21 mo, P=NS). Multivariate analysis revealed size of largest lesion (P\u3c0.01) was correlated with decreased local control; a 1 cm increase in tumor size was associated with a 25% increased risk of local failure. Subsequent transplant (P\u3c0.01) was the remaining significant factor. Treatment modality did not remain an independent predictor of LC. Predictors of OS in multivariate analysis included age (P=0.01), prior liver treatments (HR 2.86, P\u3c0.01), size of largest lesion (P\u3c0.01), Child-Pugh stage (P\u3c0.01), portal vein thrombosis (HR 1.6, P=0.04), and subsequent liver transplant (HR 0.08, P\u3c0.01). Conclusions: These findings support the effectiveness of both MR-guided SBRT and Y90 transarterial radioembolization in locoregional management of HCC at a single institution despite clear differences in the patient cohorts. Though survival outcomes were comparable, local control differences favored the cohort treated by SBRT, in large part due to differences in tumor size. This data supports further investigation in a randomized study between SBRT and Y90

Evaluating Quality of Life and Functional Outcomes in Salvage Surgery for Head and Neck Cancer

Background: Unique challenges surround treatment for residual or recurrent head and neck squamous cell carcinoma (HNSCC). Of the limited treatment options for residual or recurrent HNSCC, salvage surgery is often the best option. However, salvage surgery can result in significant morbidity, affecting both quality of life (QoL) and functional outcomes. Few studies have examined QoL outcomes following salvage surgery in the setting of HNSCC. Objectives: To analyze head and neck related quality of life and functional outcomes in patients with head and neck cancer who underwent salvage surgery. Methods: In this IRB approved study, FACT-HN Version 4 was administered pre-operatively and 6 months post-operatively to patients undergoing salvage surgery for HNSCC between November 4, 2014 and April 27, 2020. Retrospective cohort analysis was performed on this population with major outcome being postoperative QoL score. Functional outcomes included postoperative tracheostomy and feeding tube status. QoL outcomes were compared with paired t-tests. Univariate logistic regression was used to determine characteristics associated with presence of permanent tracheostomy and feeding tube, defined as presence greater than 30 days. Results: Overall, 25 patients undergoing salvage surgery for HNSCC were included in this analysis. Primary tumor sites were larynx/hypopharynx (44.0%), oral cavity (24.0%), oropharynx (20.0%), salivary (4.0%), skin (4.0%), and unknown primary (4.0%). Salvage surgeries consisted of total laryngectomy (36.0%), definitive neck dissection (24.0%), mandibulectomy (16.0%), parotidectomy (8.0%), with total laryngectomy/total glossectomy, radical tonsillectomy, TORS base of tongue excision, and transoral laser laryngeal excision all comprising 4% of cases. Total QoL scores were not significantly different preoperatively to postoperatively (mean 108.7, 95% CI=97.7 to 119.7 vs. 103.8, 95% CI: 93.1 to 114.5; P=0.436, with maximum total score of 148). Patients with lower preoperative Emotional Well-Being (EWB) subscores demonstrated significantly worse EWB subscores postoperatively (postoperative mean: 17.0, 95% CI: 14.5 to 19.4 vs. 21.7, 95% CI: 20.0 to 23.4; P=0.002). Of patients who underwent tracheostomy tube placement, 53.8% (N=7/13) remained tracheostomy dependent long-term (\u3e30 d). Of patients who underwent feeding tube placement, 81.0% (N=17/21) remained feeding tube dependent long-term (\u3e30 d). Tracheostomy and feeding tubes remained in place with median durations of 3.02 months (range 0.16 to 20.55) and 10.13 months (range 0 to 24.89), respectively. All patients with T3/4 disease undergoing salvage surgery required long-term feeding tube (N=6). Conclusions: This study provides important information about quality of life and functional outcomes for patients undergoing salvage surgery for HNSCC. There is a high rate of long-term tracheostomy and feeding tube dependence following salvage surgery. While no difference was found in head and neck related quality of life total score and sub-scores at 6 months postoperatively, general emotional well-being preoperatively was most associated with general emotional well-being postoperatively. This information should be taken into consideration when counseling and managing patients with residual or recurrent HNSCC