Trends in Computer-Aided Diagnosis Using Deep 2 Learning Techniques: A Review of Recent Studies on 3 Algorithm Development 4

With recent focus on deep neural network architectures for development of algorithms for computer-aided diagnosis (CAD), we provide a review of studies within the last 3 years (2015-2017) reported in selected top journals and conferences. 29 studies that met our inclusion criteria were reviewed to identify trends in this field and to inform future development. Studies have focused mostly on cancer-related diseases within internal medicine while diseases within gender-/age-focused fields like gynaecology/pediatrics have not received much focus. All reviewed studies employed image datasets, mostly sourced from publicly available databases (55.2%) and few based on data from human subjects (31%) and non-medical datasets (13.8%), while CNN architecture was employed in most (70%) of the studies. Confirmation of the effect of data manipulation on quality of output and adoption of multi-class rather than binary classification also require more focus. Future studies should leverage collaborations with medical experts to aid future with actual clinical testing with reporting based on some generally applicable index to enable comparison. Our next steps on plans for CAD development for osteoarthritis (OA), with plans to consider multi-class classification and comparison across deep learning approaches and unsupervised architectures were also highlighted

Investigation of hypoxia in syngeneic rat prostate tumors after irradiation with photons or carbon ions by multimodal imaging and histology

Tumor hypoxia has been widely recognized as a significant factor that increases treatment resistance and promotes malignant progression. High linear energy transfer (LET) radiotherapy (RT), e.g. with carbon ions (12C-ions), is expected to overcome this resistance factors as its lethality is less dependent on tumor oxygenation as compared to conventional low LET photon irradiation. However, the exact interplay between irradiation response, vascular changes, perfusion, and hypoxia is still not well understood, especially with respect to high LET RT. In the present thesis, the hypoxic status of syngeneic Dunning R3327 rat prostate tumor model sublines was characterized prior to and after irradiation with either low LET photons or high LET 12C-ions by multimodal imaging and histology. The initial oxygenation status of three subcutaneously transplanted Dunning tumor sublines (H, HI and AT1) was determined by photoacoustic imaging (PAI) which included the development and validation of a new PAI analysis protocol. The new protocol enabled the distinction of the three sublines based on their oxygenation profiles and their response towards external changes in oxygen supply. Subsequently, the effects of curative and sub-curative single dose irradiations with either photons or 12C-ions on the two hypoxic tumor sublines (HI and AT1) were investigated by pharmacokinetic modeling of longitudinal dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data. For this, a novel method for estimating the contrast agent’s arrival time was developed in cooperation with the group for Image Analysis and Learning of the Interdisciplinary Center for Scientific Computing of Heidelberg University. It enables a delay correction of the contrast agent arrival time which improves fit accuracy and the reliability of the pharmacokinetic modeling results. The moderately differentiated HI-tumor showed increased vascular permeability 7 days after irradiation without any modality or dose dependency, while the anaplastic and chronic hypoxic AT1-tumor revealed an earlier and stronger treatment response after 12C-ion irradiation as compared to the more delayed response after photon irradiation. Again, no dose dependency was detected. Finally, a longitudinal histology study after irradiation of the AT1-tumor with curative doses of either photons or 12C-ions revealed that hypoxia developed slightly faster after 12C-ion than after photon irradiation. Furthermore, this study validated the relative biological effectiveness (RBE) for 12C-ions, which was determined previously for the endpoint local tumor control, on a microscopic level within the first 10 days. Additionally, reasonable time points for a future multimodal imaging study with PAI, sequential positron emission tomography (PET) and DCE-MRI measurements as well as histology were determined. In conclusion, this thesis proved PAI and the novel analysis protocol to be a feasible method for the characterization of the three Dunning tumor sublines with respect to their oxygenation. The different sensitivities of the HI- and AT1-tumors towards the two irradiation modalities indicate that the irradiation-induced vascular response depends on the structural-functional status of the tumor vasculature. The dose-independent response of both tumor sublines towards the two irradiation modalities suggests that the initial vascular response only plays a minor role with respect to local tumor control at high single doses

Pheochromocytoma (PHEO) and Paraganglioma (PGL)

This book outlines some new advances in genetics, clinical evaluation, localization, therapy (newly including immunotherapy) of pheochromocytoma and paraganglioma including their metastatic counterparts. Well-known and experienced clinicians and scientists contributed to this book to include some novel approaches to these tumors. This book will serve to various health care professionals from different subspecialties, but mainly oncologists, endocrinologists, endocrine surgeons, pediatricians, and radiologists. This book shows that the field of pheochromocytoma/paraganglioma is evolving and a significant progress has been made in last 5 years requiring that health care professionals and scientists will learns new information and implement it in their clinical practice or scientific work, respectively. This book should not be missed by anybody who is focusing on neuroendocrine tumors, their newest evaluation and treatment

EXPANSION AND CHARACTERIZATION OF HUMAN BREAST CIRCULATING CANCER CELLS

Ph.DPH.D. IN MECHANOBIOLOGY (NGS

Central Nervous System Tumors

Though the treatment of central nervous system (CNS) tumors has been challenging, new advances have helped us better understand the molecular and genetic makeup of many tumor types, and new chemotherapies and immunotherapies have extended survival in patients with aggressive primary CNS tumors. This book discusses pediatric and adult tumors of the CNS, the classification schemes used to categorize them, advances in surgical techniques, and several important genetic alterations found in these tumors. We hope this book contributes to the reader’s understanding of these tumors and provides the most up-to-date and cutting-edge discoveries in this exciting field

Molecular Imaging of Prostate Cancer

Chapter 1 addresses the introduction to the thesis and provides epidemiology, etiology, metastatic spread, current diagnostics and clinical need of new biomarker for risk stratification of prostate cancer. Chapter 2 provides a detailed analysis of the distribution pattern of the three most used choline tracers: 18F-methylcholine, 11C-choline, and 18F-ethylcholine in metabolically and anatomically disease-free patients. The ranges of SUVmax, SUVmean and standard deviations have been presented. Potential pitfalls in evaluation of “non-avid” but clinically significant presentation of different disease entities are also addressed. The chapter provides overview of the variations in choline uptake pattern which is vital for assessment of various organs when imaging is performed for evaluation of metastatic disease. Chapter 3 presents the feasibility of assessing dynamic 18F Ethyl Choline PET with a view to do kinetic modelling in clinical setting of biochemical relapse of Prostate Cancer. This critical piece of work underpins the quantification, tracer kinetics and demonstrates that cancerous tissue shows abnormal perfusion. From these observations I was able to conclude that 18F Choline can act as a biomarker to assess angiogenesis in prostate cancer and introduces 18F Choline as a biomarker for further work presented in chapter 4-8. Chapter 4 addresses the detection of clinically significant and insignificant prostate cancer on 18F-FECH PET/CT and I correlated findings with template guided prostate mapping biopsy (TPM). Sensitivity and Specificity data of 8F-FECH PET/CT has been provided. Chapter 5 addresses the accuracy of 18F Choline PET/MR which is compared to reference standard (template guided prostate mapping biopsy). This work suggests that data obtained from 18F Choline PET/MR can allow detection of clinically significant and insignificant prostate cancer. I noted that multiple previous treatments can give false positive results and 18F Choline PET/MR is the imaging investigation of choice post HIFU. Moreover, false negative results with 18F Choline PET/MR can be due to very small volume (=/<2 mm) disease. Chapter 6 presents the differential diagnosis of abnormal tracer accumulation in the Prostate and periprostatic tissue. Chapter 7 provides spectrum of skeletal findings on dual-phase 18F-fluoroethylcholine (FECH) PET/CT performed during the work-up of patients referred for suspected prostate cancer relapse. I have provided quantification data and explained that SUVmax in isolation cannot be used to characterize these lesions as benign or malignant. Minimal overlap of benign and malignant lesions also exists. Chapter 8 addresses the clinical utility of 18F Choline in the setting of clinical trial in collaboration with Uro-oncology, Nuclear Medicine and Radiology departments. This critical work compares 18F Choline PET-CT and Whole-Body MRI in assessment and decision-making process for salvage treatment of focal radio-recurrent prostate cancer. This chapters concludes that at present WB-MRI cannot be used alone as imaging modality for investigation of biochemical relapse of Prostate Cancer. Chapter 9 is a summary of main findings and discussions from chapters in this thesis. It also highlights the potential applications and future perspectives of novel biomarkers for imaging of prostate cancer