Dynamic X-ray elastography using a pulsed photocathode source

X-ray absorption of breast cancers and surrounding healthy tissue can be very similar, a situation that sometimes leads to missed cancers or false-positive diagnoses. To increase the accuracy of mammography and breast tomosynthesis, we describe dynamic X-ray elastography using a novel pulsed X-ray source. This new imaging modality provides both absorption and mechanical properties of the imaged material. We use a small acoustic speaker to vibrate the sample while a synchronously pulsed cold cathode X-ray source images the mechanical deformation. Using these stroboscopic images, we derive two-dimensional stiffness maps of the sample in addition to the conventional X-ray image. In a breast phantom composed of ZrO2 powder embedded in gel, dynamic elastography derived stiffness maps were able to discriminate a hard inclusion from surrounding material with a contrast-to-noise ratio (CNR) of 4.5. The CNR on the corresponding absorption image was 1.1. This demonstrates the feasibility of dynamic X-ray elastography with a synchronously pulsed X-ray source.

Distinct nitrogen isotopic compositions of healthy and cancerous tissue in mice brain and head&neck micro-biopsies

Background Cancerous cells can recycle metabolic ammonium for their growth. As this ammonium has a low nitrogen isotope ratio (15N/14N), its recycling may cause cancer tissue to have lower 15N/14N than surrounding healthy tissue. We investigated whether, within a given tissue type in individual mice, tumoral and healthy tissues could be distinguished based on their 15N/14N. Methods Micro-biopsies of murine tumors and adjacent tissues were analyzed for 15N/14N using novel high-sensitivity methods. Isotopic analysis was pursued in Nude and C57BL/6 mice models with mature orthotopic brain and head&neck tumors generated by implantation of H454 and MEERL95 murine cells, respectively. Results In the 7 mice analyzed, the brain tumors had distinctly lower 15N/14N than healthy neural tissue. In the 5 mice with head&neck tumors, the difference was smaller and more variable. This was at least partly due to infiltration of healthy head&neck tissue by tumor cells. However, it may also indicate that the 15N/14N difference between tumoral and healthy tissue depends on the nitrogen metabolism of the healthy organ in question. Conclusions The findings, coupled with the high sensitivity of the 15N/14N measurement method used here, suggest a new approach for micro-biopsy-based diagnosis of malignancy as well as an avenue for investigation of cancer metabolism.

A thermal dose controller for laser interstitial thermal therapy

Laser interstitial thermal therapy (LITT) is a minimally invasive technique for destroying localized solid tumors by heating with light. An obstacle to widespread adoption of LITT is the lack of adequate control of heating of surrounding healthy tissue and prevention of tissue and fiber-tip charring. An LITT thermal dose controller was developed to address these issues. The goal of the controller is to deliver prescribed thermal dose at a target location in tissue in a present treatment time. The developed feedback controller has a cascade structure with primary thermal dose control loop continuously generating the reference temperature for the secondary, constrained, model predictive temperature controller. The performance of controller was evaluated in simulated linear and non-linear tissue models and in albumen phantoms. The control system demonstrated the ability to achieve treatment goals across all evaluation models by delivering 240 eq. min dose at 5 mm in various preset treatment times.

A thermal dose controller for laser interstitial thermal therapy

Laser interstitial thermal therapy (LITT) is a minimally invasive technique for destroying localized solid tumors by heating with light. An obstacle to widespread adoption of LITT is the lack of adequate control of heating of surrounding healthy tissue and prevention of tissue and fiber-tip charring. An LITT thermal dose controller was developed to address these issues. The goal of the controller is to deliver prescribed thermal dose at a target location in tissue in a present treatment time. The developed feedback controller has a cascade structure with primary thermal dose control loop continuously generating the reference temperature for the secondary, constrained, model predictive temperature controller. The performance of controller was evaluated in simulated linear and non-linear tissue models and in albumen phantoms. The control system demonstrated the ability to achieve treatment goals across all evaluation models by delivering 240 eq. min dose at 5 mm in various preset treatment times.

Ex-Vivo Detection of Breast Cancer with a Bio-Impedance Sensor

Bioimpedance is the opposition to flow of an applied electrical current through biological tissues1. Our research group designed and fabricated bipolar micro-sensors on the tip of a silicone probe, capable of measuring biological tissue impedance. It is known that the bioimpedance of cultured cancer cells differs substantially from that of healthy cell lines. We hypothesised that the bioimpedance of cancer in surgically excised human tissue would be significantly different to surrounding healthy tissue. To test this hypothesis, we designed a study to evaluate the bioimpedance of healthy and diseased breast tissue in surgically excised breast specimens. This manuscript reports the outcome of this study.

Insulin signaling mediates neurodegeneration in glioma

Cell to cell communication facilitates tissue development and physiology. Under pathological conditions, brain tumors disrupt glia-neuron communication signals that in consequence, promote tumor expansion at the expense of surrounding healthy tissue. The glioblastoma is one of the most aggressive and frequent primary brain tumors. This type of glioma expands and infiltrates into the brain, causing neuronal degeneration and neurological decay, among other symptoms. Here, we describe in a Drosophila model how glioblastoma cells produce ImpL2, an antagonist of the insulin pathway, which targets neighboring neurons and causes mitochondrial disruption as well as synapse loss, both early symptoms of neurodegeneration. Furthermore, glioblastoma progression requires insulin pathway attenuation in neurons. Restoration of neuronal insulin activity is sufficient to rescue synapse loss and to delay the premature death caused by glioma. Therefore, signals from glioblastoma to neuron emerge as a potential field of study to prevent neurodegeneration and to develop anti-tumoral strategies.

Nanoparticles in enhancing microwave imaging and microwave Hyperthermia effect for liver cancer treatment

Hyperthermia therapy is a promising therapy for liver cancer treatment that utilizes external electromagnetic waves to heat the tumor zone to preferentially kill or minimize cancer cells. Nevertheless, it’s a challenge to realize localized heating of the cancer tissue without harming the surrounding healthy tissue. This research proposes to utilize nanoparticles as microwave absorbers to enhance microwave imaging and achieve localized hyperthermia therapy. A realistic 3D abdomen model has been segmented using 3D Slicer segmentation software, and then the obtained segmented CAD model exported to Computer Simulation Technology (CST STUDIO) for applying the Finite Element Modeling (FEM). Next investigating both imaging and treatment capability. Finally, the specific absorption rate (SAR) and temperature distribution were computed without nanoparticles and with different types of nanoparticles such as gold (GNPs) and silver nanoparticles at frequency 915 MHz. By comparing the achived results, it was seen that Silver nanoparticles can make a great enhancement in raising the temperature. However, this result was unsatisfactory but, after adding gold nanoparticles the temperature exceed 42°C, at frequency 915 MHz which is achieving the hyperthermia treatment without harming the nearby healthy tissue, GNPs also can achieve a great enhancement in SAR result

Molecular Investigation on a Triple Negative Breast Cancer Xenograft Model Exposed to Proton Beams

Specific breast cancer (BC) subtypes are associated with bad prognoses due to the absence of successful treatment plans. The triple-negative breast cancer (TNBC) subtype, with estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER2) negative receptor status, is a clinical challenge for oncologists, because of its aggressiveness and the absence of effective therapies. In addition, proton therapy (PT) represents an effective treatment against both inaccessible area located or conventional radiotherapy (RT)-resistant cancers, becoming a promising therapeutic choice for TNBC. Our study aimed to analyze the in vivo molecular response to PT and its efficacy in a MDA-MB-231 TNBC xenograft model. TNBC xenograft models were irradiated with 2, 6 and 9 Gy of PT. Gene expression profile (GEP) analyses and immunohistochemical assay (IHC) were performed to highlight specific pathways and key molecules involved in cell response to the radiation. GEP analysis revealed in depth the molecular response to PT, showing a considerable immune response, cell cycle and stem cell process regulation. Only the dose of 9 Gy shifted the balance toward pro-death signaling as a dose escalation which can be easily performed using proton beams, which permit targeting tumors while avoiding damage to the surrounding healthy tissue.

Modulation of nanoparticle uptake, intracellular distribution, and retention with docetaxel to enhance radiotherapy

Objective: One of the major issues in current radiotherapy (RT) is the normal tissue toxicity. A smart combination of agents within the tumor would allow lowering the RT dose required while minimizing the damage to healthy tissue surrounding the tumor. We chose gold nanoparticles (GNPs) and docetaxel (DTX) as our choice of two radiosensitizing agents. They have a different mechanism of action which could lead to a synergistic effect. Our first goal was to assess the variation in GNP uptake, distribution, and retention in the presence of DTX. Our second goal was to assess the therapeutic results of the triple combination, RT/GNPs/DTX. Methods: We used HeLa and MDA-MB-231 cells for our study. Cells were incubated with GNPs (0.2 nM) in the absence and presence of DTX (50 nM) for 24 h to determine uptake, distribution, and retention of NPs. For RT experiments, treated cells were given a 2 Gy dose of 6 MV photons using a linear accelerator. Results: Concurrent treatment of DTX and GNPs resulted in over 85% retention of GNPs in tumor cells. DTX treatment also forced GNPs to be closer to the most important target, the nucleus, resulting in a decrease in cell survival and increase in DNA damage with the triple combination of RT/ GNPs/DTX vs RT/DTX. Our experimental therapeutic results were supported by Monte Carlo simulations. Conclusion: The ability to not only trap GNPs at clinically feasible doses but also to retain them within the cells could lead to meaningful fractionated treatments in future combined cancer therapy. Furthermore, the suggested triple combination of RT/GNPs/DTX may allow lowering the RT dose to spare surrounding healthy tissue. Advances in knowledge: This is the first study to show intracellular GNP transport disruption by DTX, and its advantage in radiosensitization.