Shedding Light on Colorectal Cancer: An In Vivo Raman Spectroscopy Approach Combined with Deep Learning Analysis.

Raman spectroscopy has emerged as a powerful tool in medical, biochemical, and biological research with high specificity, sensitivity, and spatial and temporal resolution. Recent advanced Raman systems, such as portable Raman systems and fiber-optic probes, provide the potential for accurate in vivo discrimination between healthy and cancerous tissues. In our study, a portable Raman probe spectrometer was tested in immunosuppressed mice for the in vivo localization of colorectal cancer malignancies from normal tissue margins. The acquired Raman spectra were preprocessed, and principal component analysis (PCA) was performed to facilitate discrimination between malignant and normal tissues and to highlight their biochemical differences using loading plots. A transfer learning model based on a one-dimensional convolutional neural network (1D-CNN) was employed for the Raman spectra data to assess the classification accuracy of Raman spectra in live animals. The 1D-CNN model yielded an 89.9% accuracy and 91.4% precision in tissue classification. Our results contribute to the field of Raman spectroscopy in cancer diagnosis, highlighting its promising role within clinical applications.

Nanoparticle-Mediated Radiotherapy: Unraveling Dose Enhancement and Apoptotic Responses in Cancer and Normal Cell Lines.

Cervical cancer remains a pressing global health concern, necessitating advanced therapeutic strategies. Radiotherapy, a fundamental treatment modality, has faced challenges such as targeted dose deposition and radiation exposure to healthy tissues, limiting optimal outcomes. To address these hurdles, nanomaterials, specifically gold nanoparticles (AuNPs), have emerged as a promising avenue. This study delves into the realm of cervical cancer radiotherapy through the meticulous exploration of AuNPs' impact. Utilizing ex vivo experiments involving cell lines, this research dissected intricate radiobiological interactions. Detailed scrutiny of cell survival curves, dose enhancement factors (DEFs), and apoptosis in both cancer and normal cervical cells revealed profound insights. The outcomes showcased the substantial enhancement of radiation responses in cancer cells following AuNP treatment, resulting in heightened cell death and apoptotic levels. Significantly, the most pronounced effects were observed 24 h post-irradiation, emphasizing the pivotal role of timing in AuNPs' efficacy. Importantly, AuNPs exhibited targeted precision, selectively impacting cancer cells while preserving normal cells. This study illuminates the potential of AuNPs as potent radiosensitizers in cervical cancer therapy, offering a tailored and efficient approach. Through meticulous ex vivo experimentation, this research expands our comprehension of the complex dynamics between AuNPs and cells, laying the foundation for their optimized clinical utilization.

Extended Analysis of Raman Spectra Using Artificial Intelligence Techniques for Colorectal Abnormality Classification.

Raman spectroscopy (RS) techniques are attracting attention in the medical field as a promising tool for real-time biochemical analyses. The integration of artificial intelligence (AI) algorithms with RS has greatly enhanced its ability to accurately classify spectral data in vivo. This combination has opened up new possibilities for precise and efficient analysis in medical applications. In this study, healthy and cancerous specimens from 22 patients who underwent open colorectal surgery were collected. By using these spectral data, we investigate an optimal preprocessing pipeline for statistical analysis using AI techniques. This exploration entails proposing preprocessing methods and algorithms to enhance classification outcomes. The research encompasses a thorough ablation study comparing machine learning and deep learning algorithms toward the advancement of the clinical applicability of RS. The results indicate substantial accuracy improvements using techniques like baseline correction, L2 normalization, filtering, and PCA, yielding an overall accuracy enhancement of 15.8%. In comparing various algorithms, machine learning models, such as XGBoost and Random Forest, demonstrate effectiveness in classifying both normal and abnormal tissues. Similarly, deep learning models, such as 1D-Resnet and particularly the 1D-CNN model, exhibit superior performance in classifying abnormal cases. This research contributes valuable insights into the integration of AI in medical diagnostics and expands the potential of RS methods for achieving accurate malignancy classification.

Patient Dose Estimation in Computed Tomography-Guided Biopsy Procedures.

This study establishes typical Diagnostic Reference Levels (DRL) values and assesses patient doses in computed tomography (CT)-guided biopsy procedures. The Effective Dose (ED), Entrance Skin Dose (ESD), and Size-Specific Dose Estimate (SSDE) were calculated using the relevant literature-derived conversion factors. A retrospective analysis of 226 CT-guided biopsies across five categories (Iliac bone, liver, lung, mediastinum, and para-aortic lymph nodes) was conducted. Typical DRL values were computed as median distributions, following guidelines from the International Commission on Radiological Protection (ICRP) Publication 135. DRLs for helical mode CT acquisitions were set at 9.7 mGy for Iliac bone, 8.9 mGy for liver, 8.8 mGy for lung, 7.9 mGy for mediastinal mass, and 9 mGy for para-aortic lymph nodes biopsies. In contrast, DRLs for biopsy acquisitions were 7.3 mGy, 7.7 mGy, 5.6 mGy, 5.6 mGy, and 7.4 mGy, respectively. Median SSDE values varied from 7.6 mGy to 10 mGy for biopsy acquisitions and from 11.3 mGy to 12.6 mGy for helical scans. Median ED values ranged from 1.6 mSv to 5.7 mSv for biopsy scans and from 3.9 mSv to 9.3 mSv for helical scans. The study highlights the significance of using DRLs for optimizing CT-guided biopsy procedures, revealing notable variations in radiation exposure between helical scans covering entire anatomical regions and localized biopsy acquisitions.

DIAGNOSTIC REFERENCE LEVELS AND COMPLEXITY INDICES IN INTERVENTIONAL RADIOLOGY.

The establishment of typical diagnostic reference levels (DRLs) values according to the complexity indices (CIs) for hepatic chemoembolisation (HC), iliac stent placement (ISP) and femoropopliteal revascularisation (FR) is reported in this study. To estimate patients' stochastic effects, effective dose was calculated through dose area product (DAP) values of this study and E/DAP conversion factors derived from the literature. Data for DAP, Reference Air Kerma (Ka,r) and fluoroscopy time (FT) were collected for 218 patients and CIs were assigned to each procedure to extract DRLs. To estimate effective dose, conversion factors and DAP values were used for seven IR procedures. DRL values for DAP were 141, 130 and 28 Gy*cm2 for HC, ISP, and FR, respectively. The corresponding DRL values for Ka,r were 634.6, 300.1 and 112.0 mGy, and for FT were 15.3, 12.4 and 17.9 min, respectively. CIs in interventional radiology are a useful tool for the optimisation of DRLs since they contribute to patient's doses.

Clustered DNA Damage Patterns after Proton Therapy Beam Irradiation Using Plasmid DNA.

Modeling ionizing radiation interaction with biological matter is a major scientific challenge, especially for protons that are nowadays widely used in cancer treatment. That presupposes a sound understanding of the mechanisms that take place from the early events of the induction of DNA damage. Herein, we present results of irradiation-induced complex DNA damage measurements using plasmid pBR322 along a typical Proton Treatment Plan at the MedAustron proton and carbon beam therapy facility (energy 137-198 MeV and Linear Energy Transfer (LET) range 1-9 keV/µm), by means of Agarose Gel Electrophoresis and DNA fragmentation using Atomic Force Microscopy (AFM). The induction rate Mbp-1 Gy-1 for each type of damage, single strand breaks (SSBs), double-strand breaks (DSBs), base lesions and non-DSB clusters was measured after irradiations in solutions with varying scavenging capacity containing 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris) and coumarin-3-carboxylic acid (C3CA) as scavengers. Our combined results reveal the determining role of LET and Reactive Oxygen Species (ROS) in DNA fragmentation. Furthermore, AFM used to measure apparent DNA lengths provided us with insights into the role of increasing LET in the induction of highly complex DNA damage.

FDXR Gene Expression after in Vivo Radiation Exposure of Pediatric Patients Undergoing Interventional Cardiology Procedures.

BACKGROUND: Ferredoxin reductase (FDXR) has already been reported as a promising biomarker for estimating radiation doses in radiotherapy. This study aimed to investigate the responsiveness of FDXR on pediatric population exposed to ionizing radiation (X-rays) during pediatric interventional cardiology (IC) procedures. PATIENTS AND METHODS: Peripheral blood was collected by venipuncture from 24 pediatric donors before and 24 hours after the IC procedure. To estimate the effective dose, demographic data and Air Kerma-Area Product (PKA) were recorded for each patient. The relative quantification (RQ) of the FDXR gene in irradiated patient blood samples compared to the non-irradiated blood samples was determined using qPCR analysis. The relative values of FDXR were log- transformed. RESULTS: The effective dose ranged from 0.002 mSv to 8.004 mSv. Over this radiation exposure range, the FDXR gene expression varied randomly with the effective dose. Up-regulation in FDXR expression was observed in 17 patients and down-regulation in 7 patients. CONCLUSIONS: Further studies in a larger cohort of pediatric patients along with the record of clinical data are needed to determine whether FDXR gene expression is an effective biomarker for radiation exposure estimation in pediatric imaging.

Nanomedicine approaches for treatment of hematologic and oncologic malignancies.

Cancer is a leading cause of death worldwide. Nowadays, the therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology and novel nanomedicine products represents an opportunity to achieve sophisticated targeting strategies and multi-functionality. Nanomedicine is increasingly used to develop new cancer diagnosis and treatment methods since this technology can modulate the biodistribution and the target site accumulation of chemotherapeutic drugs, thereby reducing their toxicity. Cancer nanotechnology and cancer immunotherapy are two parallel themes that have emerged over the last few decades while searching for a cure for cancer. Immunotherapy is revolutionizing cancer treatment, as it can achieve unprecedented responses in advanced-stage patients, including complete cures and long-term survival. A deeper understanding of the human immune system allows the establishment of combination regimens in which immunotherapy is combined with other treatment modalities (as in the case of the nanodrug Ferumoxytol). Furthermore, the combination of gene therapy approaches with nanotechnology that aims to silence or express cancer-relevant genes via one-time treatment is gradually progressing from bench to bedside. The most common example includes lipid-based nanoparticles that target VEGF-Α and KRAS pathways. This review focuses on nanoparticle-based platforms utilized in recent advances aiming to increase the efficacy of currently available cancer therapies. The insights provided and the evidence obtained in this paper indicate a bright future ahead for immuno-oncology applications of engineering nanomedicines.

Quantification of Nanoscale Dose Enhancement in Gold Nanoparticle-Aided External Photon Beam Radiotherapy.

The recent progress in Nanotechnology has introduced Gold Nanoparticles (AuNPs) as promising radiosensitizing agents in radiation oncology. This work aims to estimate dose enhancement due to the presence of AuNPs inside an irradiated water region through Monte Carlo calculations. The GATE platform was used to simulate 6 MV photon histories generated from a TrueBeam® linear accelerator with and without a Flattening Filter (FF) and model AuNPs clusters. The AuNPs size, concentration and distribution pattern were examined. To investigate different clinical irradiation conditions, the effect of field size, presence of FF and placement of AuNPs in water were evaluated. The range of Dose Enhancement Factors (DEF = DoseAu/DoseWater) calculated in this study is 0.99 ± 0.01-1.26 ± 0.02 depending on photon beam quality, distance from AuNPs surface, AuNPs size and concentration and pattern of distribution. The highest DEF is reported for irradiation using un-flattened photon beams and at close distances from AuNPs. The obtained findings suggest that dose deposition could be increased in regions that represent whole cells or subcellular targets (mitochondria, cell nucleus, etc.). Nevertheless, further and consistent research is needed in order to make a step toward AuNP-aided radiotherapy in clinical practice.

Raman Spectroscopy: A Personalized Decision-Making Tool on Clinicians' Hands for In Situ Cancer Diagnosis and Surgery Guidance.

Accurate in situ diagnosis and optimal surgical removal of a malignancy constitute key elements in reducing cancer-related morbidity and mortality. In surgical oncology, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. Conventional imaging techniques have attempted to serve as adjuvant tools for in situ biopsy and surgery guidance. However, no single imaging modality has been proven sufficient in terms of specificity, sensitivity, multiplexing capacity, spatial and temporal resolution. Moreover, most techniques are unable to provide information regarding the molecular tissue composition. In this review, we highlight the potential of Raman spectroscopy as a spectroscopic technique with high detection sensitivity and spatial resolution for distinguishing healthy from malignant margins in microscopic scale and in real time. A Raman spectrum constitutes an intrinsic "molecular finger-print" of the tissue and any biochemical alteration related to inflammatory or cancerous tissue state is reflected on its Raman spectral fingerprint. Nowadays, advanced Raman systems coupled with modern instrumentation devices and machine learning methods are entering the clinical arena as adjunct tools towards personalized and optimized efficacy in surgical oncology.

Ag/Au Bimetallic Nanoparticles Trigger Different Cell Death Pathways and Affect Damage Associated Molecular Pattern Release in Human Cell Lines.

Apoptosis induction is a common therapeutic approach. However, many cancer cells are resistant to apoptotic death and alternative cell death pathways including pyroptosis and necroptosis need to be triggered. At the same time, danger signals that include HMGB1 and HSP70 can be secreted/released by damaged cancer cells that boost antitumor immunity. We studied the cytotoxic effects of AgAu NPs, Ag NPs and Au NPs with regard to the programmed cell death (apoptosis, necroptosis, pyroptosis) and the secretion/release of HSP70 and HMGB1. Cancer cell lines were incubated with 30, 40 and 50 µg/mL of AgAu NPs, Ag NPs and Au NPs. Cytotoxicity was estimated using the MTS assay, and mRNA fold change of CASP1, CASP3, BCL-2, ZPB1, HMGB1, HSP70, CXCL8, CSF1, CCL20, NLRP3, IL-1ß and IL-18 was used to investigate the associated programmed cell death. Extracellular levels of HMGB1 and IL-1ß were investigated using the ELISA technique. The nanoparticles showed a dose dependent toxicity. Pyroptosis was triggered for LNCaP and MDA-MB-231 cells, and necroptosis for MDA-MB-231 cells. HCT116 cells experience apoptotic death and show increased levels of extracellular HMGB1. Our results suggest that in a manner dependent of the cellular microenvironment, AgAu NPs trigger mixed programmed cell death in P53 deficient MDA-MB-231 cells, while they also trigger IL-1ß release in MDA-MB-231 and LNCaP cells and release of HMGB1 in HCT116 cells.

Requirements for Designing an Effective Metallic Nanoparticle (NP)-Boosted Radiation Therapy (RT).

Many different tumor-targeted strategies are under development worldwide to limit the side effects and improve the effectiveness of cancer therapies. One promising method is to enhance the radiosensitization of the cancer cells while reducing or maintaining the normal tissue complication probability during radiation therapy using metallic nanoparticles (NPs). Radiotherapy with MV photons is more commonly available and applied in cancer clinics than high LET particle radiotherapy, so the addition of high-Z NPs has the potential to further increase the efficacy of photon radiotherapy in terms of NP radiosensitization. Generally, when using X-rays, mainly the inner electron shells are ionized, which creates cascades of both low and high energy Auger electrons. When using high LET particles, mainly the outer shells are ionized, which give electrons with lower energies than when using X-rays. The amount of the produced low energy electrons is higher when exposing NPs to heavy charged particles than when exposing them to X-rays. Since ions traverse the material along tracks, and therefore give rise to a much more inhomogeneous dose distributions than X-rays, there might be a need to introduce a higher number of NPs when using ions compared to when using X-rays to create enough primary and secondary electrons to get the desired dose escalations. This raises the questions of toxicity. This paper provides a review of the fundamental processes controlling the outcome of metallic NP-boosted photon beam and ion beam radiation therapy and presents some experimental procedures to study the biological effects of NPs' radiosensitization. The overview shows the need for more systematic studies of the behavior of NPs when exposed to different kinds of ionizing radiation before applying metallic-based NPs in clinical practice to improve the effect of IR therapy.

Radiation Exposure in Pediatric Interventional Procedures.

The article is part of the series of articles on radiation protection. You can find further articles in the special section of the CVIR issue. The expanding applications of interventional procedures coupled with the potential harmful effects of ionizing radiation highlight the need to assess the delivered radiation dose and establish an effective radiation protection program, particularly in the radiosensitive pediatric population. Given the complexity and heterogeneity of interventional procedures as well as the unique characteristics of children, the management of radiation dose is proving to be quite challenging. The aim of the current article is to provide an overview of the radiation exposure in pediatric patients during interventional procedures focusing on the importance of radiation protection in the pediatric population, the reported radiation doses and the techniques of minimizing radiation dose.

The Importance of Radiation Protection Education and Training for Medical Professionals of All Specialties.

The article is part of the series of articles on radiation protection. You can find further articles in the special section of the CVIR issue. Lately, more advanced techniques have been introduced in medical imaging expanding the diagnostic and therapeutic applications of ionizing radiation. Among the various strategies that have been proposed for the management of radiation exposure, education and training seem to have a strong impact on radiation protection and dose reduction. However, according to several studies, medical professionals appear to lack knowledge on basic radiation protection aspects. Therefore, the establishment of an accreditation and certification system in radiation protection for all medical professionals employing ionizing radiation is considered as high priority. The purpose of this review article is to highlight the importance of education and training in radiation protection, provide recommendations for an effective educational program and propose an educational program structure for the different medical specialties.

Monte Carlo studies in Gold Nanoparticles enhanced radiotherapy: The impact of modelled parameters in dose enhancement.

PURPOSE: Over the last decades, Gold Nanoparticles (AuNPs) have been presented as an innovative approach in radiotherapy (RT) enhancement. Several studies have proven that the irradiation of tumors containing AuNPs could lead to more effective tumor control than irradiation alone. Studies with low kV photons and AuNPs conclude in encouraging results regarding the level of radioenhancement. However, experimental and theoretical studies with MV photons report controversial findings concerning the correlation between dose enhancement effect and tumor cell killing. The great variation in the experimental protocols and simulations complicates the comparison of their outcomes and depicts the need for limiting the variety of investigated parameters. Our purpose is to point out a possible direction for building realistic Monte Carlo (MC) models that could end up with promising results in MV photons RT enhancement. METHODS: We explored published in silico studies concerning AuNPs enhanced RT from 2010 to 2019. In this review, we discuss the different AuNPs and MV photon beams characteristics that have been reported and their effect in dose enhancement. RESULTS: AuNPs size, concentration, type of distribution along with photon beams energy and the presence of flattening filter in linear accelerators seem to be the major parameters that determine AuNPs radioenhancement in silico. CONCLUSIONS: Prior to AuNPs clinical translation in photon radiotherapy, in silico studies should emphasize on nanodosimetry and track structure codes than condensed history ones. Toxicity estimation and biological aspects should be implemented in MC simulations so as to achieve accurate and realistic modelling of AuNPs driven RT.

Local diagnostic reference levels in pediatric CT examinations: a survey at the largest children's hospital in Greece.

OBJECTIVES: The increased frequency of pediatric CT examinations and the high radiosensitivity of children entail the need to determine DRLs and optimize CT protocols. The aim of the study was twofold. Firstly, to establish pediatric LDRLs according to age and weight for the most common types of CT examinations at the largest children's hospital in Greece. Secondly, to compare LDRLs with European DRLs. METHODS: A total of 756 pediatric patients who underwent head, chest, and abdomen-pelvis CT examinations were included. Patients were categorized into age groups according to the hospital's protocols. All CT examinations were performed using iterative reconstruction algorithm and AEC. LDRLs were determined in terms of 75th percentile of CTDIvol and DLP. Values of LDRLs were subsequently regrouped into weight categories and compared with European DRLs. RESULTS: Gathering all age groups for head CT examinations and all weight groups for body CT examinations, LDRLs were ranged from (22-68, 2-5, 2-10) mGy in terms of CTDIvol; (317-786, 22-168, 58-425) mGy.cm in terms of DLP per acquisition and (324-838, 42-265, 85-498) mGy.cm in terms of total DLP for head, chest and abdomen-pelvis CT examinations, respectively. CONCLUSION: CTDI LDRLs were comparable to European DRLs for head and either comparable or lower than European DRLs for body CT examinations. DLP LDRLs were higher than European DRLs for head and lower for body CT examinations. ADVANCES IN KNOWLEDGE: Age- and weight-based LDRLs for pediatric CT examinations were established for the largest children's hospital in Greece. Further investigations across the country are required for the establishment of national pediatric DRLs in Greece.

Ag/Au Bimetallic Nanoparticles Inhibit Tumor Growth and Prevent Metastasis in a Mouse Model.

PURPOSE: To evaluate the antitumor efficacy of Ag3Au1Trp1:2NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor's metastatic potential and the underlying molecular mechanism. SUBJECTS AND METHODS: Ag3Au1Trp1:2NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag3Au1Trp1:2NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively. RESULTS: In the 4T1 tumor-bearing SCID mice, Ag3Au1Trp1:2NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels. CONCLUSION: Based on our results, Ag3Au1Trp1:2NPs express anti-tumor and anti-metastatic effects in vivo. Ag3Au1Trp1:2NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway.

Proton Density Fat Suppressed MRI in 3T Increases the Sensitivity of Multiple Sclerosis Lesion Detection in the Cervical Spinal Cord.

PURPOSE: Considering the number of multiple sclerosis (MS) patients referred for clinical spinal cord imaging, the optimization of imaging protocols plays a crucial role. We aimed to evaluate the use of proton density (PD) turbo spin-echo (TSE) with spectral attenuated inversion recovery (SPAIR) fat suppression and compare it with the currently recommended T2-TSE-SPAIR in sagittal plane in cervical spinal cord imaging. METHODS: In this study 35 MS patients with clinically suspected or known spinal cord lesions were scanned on a 3.0T magnetic resonance imaging (MRI) system. In addition to the routine protocol, PD-TSE-SPAIR sequences were obtained to quantitatively and qualitatively evaluate lesion detectability and image quality compared to T2-TSE-SPAIR sequences. Quantitative analysis was based on measurements of lesion-to-cord contrast ratio (LCCR), lesion contrast-to-noise ratio (LCNR) and lesion dimensions and the qualitative analysis on ranking with a predetermined score scale. The presence of lesions in these sequences was verified in axial T2 multi-echo gradient echo images. RESULTS: In quantitative analysis, the lesions on PD-TSE-SPAIR had statistically significantly higher contrast (p < 0.05), according to the statistical test of LCCR, LCNR calculated contrast and measured lesion dimensions. Qualitative analyses were congruent with quantitative results; the median rank of PD-TSE-SPAIR was significantly higher than T2-TSE-SPAIR (p < 0.05). Of the 34 detected lesions 9 (26%) were not visualized in T2-TSE-SPAIR sequence. CONCLUSION: Considering its superiority in contrast ratios and lesion dimensions when compared to T2-TSE-SPAIR in both qualitative and quantitative analyses, we therefore recommend PD-TSE-SPAIR as a pivotal sequence to evaluate demyelinating spinal cord lesions at 3T.

Ipsilateral and contralateral cerebro-cerebellar white matter connections: A diffusion tensor imaging study in healthy adults.

BACKGROUND AND PURPOSE: The cerebellum has a pivotal role in regulating human behavior; yet whether this function is mediated only through contralateral cerebro-cerebellar pathways is under-investigated. Thus, we examined feed-backward and feed-forward ipsilateral and contralateral cerebro-cerebellar connections using a detereministic diffusion tensor imaging (DTI) algorithm, the robustness of which was also estimated using phantom DTI data. MATERIALS AND METHODS: Fifty-one healthy controls (22-60 years old; 15 males/36 females) were scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of-interest (ROI) method was applied for the reconstruction of the ipsilateral and contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC), parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto-cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally using the Brainance DTI Suite. A realistic diffusion MR phantom was used to evaluate the fiber tracking methodology for 16 fibers containing crossing, kissing, splitting and bending configurations. RESULTS: Both contralateral and ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully reconstructed; the contralateral DRTC tract was not reconstructed in all subjects. Also, the TPC tract was not reproduced in several subjects mostly regarding the contralateral connection. Descriptive DTI measures (number of fibers, fractional anisotropy, radial and axial diffusivity) are presented for each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16 fibers that almost perfectly matched the 16 ground truth fibers. CONCLUSIONS: We identified ipsilateral and contralateral connections using a clinically applicable DTI sequence, a robust deterministic algorithm and an unbiased methodology, which can be applied in daily practice in different brain pathologies.

Ag/Au bimetallic nanoparticles induce apoptosis in human cancer cell lines via P53, CASPASE-3 and BAX/BCL-2 pathways.

Au/Ag bimetallic nanoparticles (BNPs) exhibit a wide range of excellent electronic, chemical, biological, mechanical and thermal properties due to synergistic effects. However, critical questions regarding stability, biocompatibility and their cytotoxic effects remain to be answered. In this study, Ag/Au BNPs have been synthesized as "alloy" via a chemical reduction method using double molar excess of tryptophan [ν(M):ν(Trp) = 1:2]. We then estimated their toxicity in HCT116, 4T1, HUH7 and HEK293 cell lines in monocellular and spheroid cultures. Ag/Au nanoparticles with metal ratio 3:1, had the maximal antitumor effect in cancer cell lines, while the toxicity was found significantly decreased in non-cancerous cell lines. Our results were also compared to previous data regarding Ag/Au using single molar excess of tryptophan [ν(M):ν(Trp) = 1:1], suggesting that tryptophan has a protective effect on HEK293 and not in cancer cells. Aiming to investigate the molecular mechanism behind nanopartricles cytotoxicity, we studied the expression of cell cycle and apoptosis related genes on HCT116, 4T1, and HUH7 monocellular culture. Hence, we showed that bimetallic cytotoxicity is mediated via the caspase and the p53/Bax/Bcl-2 apoptotic pathway. In conclusion, our study suggests tryptophan ratio along with metal ratio used in Ag/Au BNPs as a successful way to control the toxicity in cancer cells towards non-cancerous cells, underlying the potency of bimetallic nanoparticles as selective anti-tumor agents.