Thermal ablation of biological tissues in disease treatment: A review of computational models and future directions

Percutaneous thermal ablation has proved to be an effective modality for treating both benign and malignant tumors in various tissues. Among these modalities, radiofrequency ablation (RFA) is the most promising and widely adopted approach that has been extensively studied in the past decades. Microwave ablation (MWA) is a newly emerging modality that is gaining rapid momentum due to its capability of inducing rapid heating and attaining larger ablation volumes, and its lesser susceptibility to the heat sink effects as compared to RFA. Although the goal of both these therapies is to attain cell death in the target tissue by virtue of heating above 50 oC, their underlying mechanism of action and principles greatly differs. Computational modelling is a powerful tool for studying the effect of electromagnetic interactions within the biological tissues and predicting the treatment outcomes during thermal ablative therapies. Such a priori estimation can assist the clinical practitioners during treatment planning with the goal of attaining successful tumor destruction and preservation of the surrounding healthy tissue and critical structures. This review provides current state-of- the-art developments and associated challenges in the computational modelling of thermal ablative techniques, viz., RFA and MWA, as well as touch upon several promising avenues in the modelling of laser ablation, nanoparticles assisted magnetic hyperthermia and non- invasive RFA. The application of RFA in pain relief has been extensively reviewed from modelling point of view. Additionally, future directions have also been provided to improve these models for their successful translation and integration into the hospital work flow

Innovative approaches for cancer treatment: current perspectives and new challenges

Every year, cancer is responsible for millions of deaths worldwide and, even though much progress has been achieved in medicine, there are still many issues that must be addressed in order to improve cancer therapy. For this reason, oncological research is putting a lot of effort towards finding new and efficient therapies which can alleviate critical side effects caused by conventional treatments. Different technologies are currently under evaluation in clinical trials or have been already introduced into clinical practice. While nanomedicine is contributing to the development of biocompatible materials both for diagnostic and therapeutic purposes, bioengineering of extracellular vesicles and cells derived from patients has allowed designing ad hoc systems and univocal targeting strategies. In this review, we will provide an in-depth analysis of the most innovative advances in basic and applied cancer research

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 335)

This bibliography lists 143 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during March, 1990. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance

Investigating potential nano- and micro-drug delivery systems toward the non-invasive treatment of glioblastoma brain tumours

Glioblastoma is one of the most aggressive and fatal brain tumours and is uncurable in most cases. The complete removal of glioblastoma brain tumours (GBM) is impossible by surgery alone. Despite aggressive chemotherapy and radiotherapy treatments following surgery, tumour cells continue to grow, leading to the death of patients within 15 months after diagnosis. The carnosine dipeptide is an attractive option for treating GBM, with growing numbers of studies now demonstrating its tumour accessibility, resulting in improved survival in pre-clinical GBM models. Several attempts at carnosine treatments have been developed and tested in GBM patients, however, these trials have not progressed due to the short lifetime of carnosine as a result of its enzymatic degradation in the presence of the naturally occurring carnosinase enzyme in the brain. This project aims to investigate the potential of using nano- and micro-drug delivery systems for non-invasive treatment of GBM for applying carnosine as a complementary therapy. Carnosine was successfully embedded within a carrier that can be externally triggered to release its full oncological treatment potential of the dipeptide in situ. The drug delivery device was comprised of novel nano-rod-shaped superparamagnetic iron oxide nanoparticles (ca. 86 × 19 × 11 nm) capped with a branched polyethyleneimine, capable of loading carnosine. The therapeutic agent was released by the drug delivery carrier in the presence of heat or a rotating magnetic field, as an external trigger. The new drug delivery system was characterised using electron microscopy, dynamic light scattering, elemental analysis, and magnetic resonance imaging (MRI) techniques. In addition, the cytotoxicity studies were also investigated which enabled the determination of the safety margin of applying the coated iron oxide nanorods on U87 MG cells. To determine the effectiveness of the carnosine delivery systems as a treatment for glioblastoma, the coated iron oxide nanorods were screened in vitro using the U87 MG human glioblastoma astrocytoma cell line. Labile carnosine (100 mM) was determined to suppress the proliferation and mobility of U87 MG cells within 48 hours, significantly reducing migration and potential metastasis. The cytotoxicity studies enabled calculating the half maximal inhibitory concentration (IC50) and the half maximal effective concentration (EC50) of the carnosine. The active carnosine was found to be fully released from the carrier, with only mild hyperthermia conditions at 40 ˚C being necessary. This is achievable in clinical applications, for both sustained and triggered release treatment of glioblastoma brain tumours, utilising the paramagnetic properties of iron oxide nanorods. This demonstrates the potential to inhibit post-surgery metastasis with the benefit of non-invasive monitoring via MRI scanning. The controlled release of carnosine treatment was also inspected by applying external trigger. Therefore, the nano-rod-shaped superparamagnetic iron oxide and the carnosine were encapsulated inside poly(lactic-co-glycolic acid) beads (10 μm) using a hydrodynamic microfluidic flow focusing system, and the formulation was characterised by scanning and transmission electron microscopy (SEM, TEM) and Fourier-transform infrared spectroscopy (FT-IR). A non-heating rotating magnetic field (Halbach magnet array, 1 Tesla, 20 Hz, 30 min) was utilised to stimulate the release of carnosine from the polymeric beads by rotating the nano rods from distance. Additional potential treatment in intranasal application was also investigated via a spray device. The microfluidic flow focusing system was utilised to encapsulate the carnosine therapeutic inside a liposome (ca. 300 nm diameter) matrix with a stability profile of 30 days. The sub-microscale size of the liposomes and the mucoadhesive properties were expected to enhance the nasal bioavailability of carnosine over a prolonged time. The liposomal formulation was optimised to load the carnosine (75% w/w). The characterisation of the liposomes was confirmed via microscopic imaging, dynamic light scattering (DLS), Liquid chromatography–mass spectrometry (LC-MS), and Fourier-transform infrared spectroscopy (FT-IR). The stability and sustained release profiles were investigated using physicochemical studies of membrane dialysis over time. The carnosine-loaded liposomes were stable (30 days at 8 ˚C) as a ready-to-use suspension for intranasal spray application. Overall, these results provide a promising optimised formula for complementary carnosine treatment, which is recommended to be studied in vivo in rat models in the near future. Spheroids, a complex 3-dimensional (3D) structure, resemble in vivo tumour growth more closely. As part of this project, a protocol has been developed towards a rapid and high throughput method for the generation of single spheroids using various cancer cell lines, including different cancer cells (U87 MG, SEBTA-027, SF188), prostate cancer cells (DU-145, TRAMP-C1) and breast cancer cells (BT-549, Py230) in 96-round bottom well plates. The proposed method was associated with significantly low costs per plate without the need for refining or transferring. The homogeneous compact spheroid morphology was evidenced within one day after following this new protocol. Proliferating cells, on the surface of the spheroid, were traced using confocal microscopy and the Incucyte® live cell analysis system. In contrast, dead cells were found to be located inside the core region of the spheroid. Hematoxylin and eosin (H&E) staining of spheroid sections was utilised to investigate the tightness of the cell packaging. This method enabled the determination of the EC50 of the anti-cancer dipeptide carnosine on a U87 MG 3D culture. This new protocol allows for the robust generation of various uniform spheroids that show 3D morphological characteristics. As such, further studies will be developed towards an in vivo animal model to demonstrate the potential clinical viability of this work on various cancer types, such as brain and prostate tumours

RFA Guardian: Comprehensive Simulation of Radiofrequency Ablation Treatment of Liver Tumors

The RFA Guardian is a comprehensive application for high-performance patient-specific simulation of radiofrequency ablation of liver tumors. We address a wide range of usage scenarios. These include pre-interventional planning, sampling of the parameter space for uncertainty estimation, treatment evaluation and, in the worst case, failure analysis. The RFA Guardian is the first of its kind that exhibits sufficient performance for simulating treatment outcomes during the intervention. We achieve this by combining a large number of high-performance image processing, biomechanical simulation and visualization techniques into a generalized technical workflow. Further, we wrap the feature set into a single, integrated application, which exploits all available resources of standard consumer hardware, including massively parallel computing on graphics processing units. This allows us to predict or reproduce treatment outcomes on a single personal computer with high computational performance and high accuracy. The resulting low demand for infrastructure enables easy and cost-efficient integration into the clinical routine. We present a number of evaluation cases from the clinical practice where users performed the whole technical workflow from patient-specific modeling to final validation and highlight the opportunities arising from our fast, accurate prediction techniques

A Patient-Specific Infrared Imaging Technique for Adjunctive Breast Cancer Screening: A Clinical and Simulation - Based Approach

Breast cancer is currently the most prevalent form of cancer in women with over 266,000 new diagnoses every year. The various methods used for breast cancer screening range in accuracy and cost, however there is no easily reproducible, reliable, low-cost screening method currently available for detecting cancer in breasts, especially with dense tissue. Steady-state Infrared Imaging (IRI) is unaffected by tissue density and has the potential to detect tumors in the breast by measuring and capturing the thermal profile on the breast surface induced by increased blood perfusion and metabolic activity in a rapidly growing malignant tumor. The current work presents a better understanding of IRI as an accurate breast cancer detection modality. A detailed study utilizing IRI-MRI approach with clinical design and validation of an elaborate IRI-Mammo study are presented by considering patient population, clinical study design, image interpretation, and recommended future path. Clinical IRI images are obtained in this study and an ANSYS-based modeling process developed earlier at RIT is used to localize and detect tumor in seven patients without subjective human interpretation. Further, the unique thermal characteristics of tumors that make their signatures distinct from benign conditions are identified. This work is part of an ongoing multidisciplinary collaboration between a team of thermal engineers and numerical modelers at the Rochester Institute of Technology and a team of clinicians at the Rochester General Hospital. The following components were developed to ensure valid experimentation while considering ethical considerations: IRB documentation, patient protocols, an image acquisition system (camera setup and screening table), and the necessary tools needed for image analysis without human interpretation. IRI images in the prone position were obtained and were used in accurately detecting the presence of a cancerous tumor in seven subjects. The size and location of tumor was also confirmed within 7 mm as compared to biopsy-proven pathology information. The study indicates that the IRI-Mammo approach has potential to be a highly effective adjunctive screening tool that can improve the breast cancer detection rates especially for subjects with dense breast tissue. This method is low cost, no-touch, radiation-free and highly portable, making it an attractive candidate as a breast cancer detection modality. Further, the developed method provided insight into infrared features corresponding to other biological images, pathology reports and patient history

Interstitial diagnosis and treatment of breast tumours

This thesis exploits the interaction of light with breast tissue for diagnosis and therapy. Optical biopsy is an experimental technique, based on Elastic Scattering Spectroscopy (ESS), being developed for characterising breast tissue. An optical probe interrogates tissue with a white light pulse, with spectral analysis of the reflected light. 264 spectral measurements (50 patients) were obtained from a range of breast tissues and axillary lymph nodes and correlated with conventional histology of biopsies from the same sites. Algorithms for spectral analysis were developed using ANN (Artificial Neural Network), HCA (Hierarchical Cluster Analysis) and MBA (Model Based Analysis). The sensitivity and specificity for cancer detection in breast and lymph nodes were: [diagram]. Interstitial Laser Photocoagulation (ILP) involves image guided, thermal coagulation of lesions within the breast using laser energy delivered via optical fibres positioned percutaneously under local anaesthetic. Two groups were studied: 1) Nineteen patients with benign fibroadenomas underwent ILP and the results compared with 11 treated conservatively. Thirteen ILP patients (14 fibroadenomas) and 6 controls (11 fibroadenomas) have reached their one-year review: [diagram]. These differences are statistically significant (P<0.001). 2)Six patients with primary breast cancers underwent ILP (with pre- and post-ILP contrast enhanced MRI) within 3 weeks of diagnosis and were then treated with Tamoxifen. Four underwent surgery at 3 months, two showing complete tumour ablation. MRI was reasonably accurate at detecting residual tumour. In conclusion: a) optical biopsy is a promising 'real time' diagnostic tool for breast disease. b) ILP could provide a simple and safe alternative to surgery for fibroadenomas. c) ILP with MRI monitoring may be an alternative to surgery in the management of some patients with localised primary breast cance

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

To mark the recent advances in nanomaterials and nanotechnology in biomedical imaging and cancer therapy, this book, entitled Application of Nanomaterials in Biomedical Imaging and Cancer Therapy includes a collection of important nanomaterial studies on medical imaging and therapy. The book covers recent works on hyperthermia, external beam radiotherapy, MRI-guided radiotherapy, immunotherapy, photothermal therapy, and photodynamic therapy, as well as medical imaging, including high-contrast and deep-tissue imaging, quantum sensing, super-resolution microscopy, and three-dimensional correlative light and electron microscopy. The significant research results and findings explored in this work are expected to help students, researchers and teachers working in the field of nanomaterials and nanotechnology in biomedical physics, to keep pace with the rapid development and the applications of nanomaterials in precise imaging and targeted therapy

Insights into infusion-based targeted drug delivery in brain: perspectives, challenges and opportunities

Targeted drug delivery in the brain is instrumental in the treatment of lethal brain diseases, such as glioblastoma multiforme, the most aggressive primary central nervous system tumour in adults. Infusion-based drug delivery techniques, which directly administer to the tissue for local treatment, as in convection-enhanced delivery (CED), provide an important opportunity; however, poor understanding of the pressure-driven drug transport mechanisms in the brain has hindered its ultimate success in clinical applications. In this review, we focus on the biomechanical and biochemical aspects of infusion-based targeted drug delivery in the brain and look into the underlying molecular level mechanisms. We discuss recent advances and challenges in the complementary field of medical robotics and its use in targeted drug delivery in the brain. A critical overview of current research in these areas and their clinical implications is provided. This review delivers new ideas and perspectives for further studies of targeted drug delivery in the brain