In vitroassessment of a gallium-doped glass polyalkenoate cement: chemotherapeutic potential, cytotoxicity and osteogenic effects.

Metastatic bone lesions are often osteolytic, which causes advanced-stage cancer sufferers to experience severe pain and an increased risk of developing a pathological fracture. Gallium (Ga) ion possesses antineoplastic and anti-bone resorption properties, suggesting the potential for its local administration to impede the growth of metastatic bone lesions. This study investigated the chemotherapeutic potential, cytotoxicity, and osteogenic effects of a Ga-doped glass polyalkenoate cement (GPC) (C-TA2) compared to its non-gallium (C-TA0) counterpart. Ion release profiles revealed a biphasic pattern characterized by an initial burst followed by a gradually declining release of ions. C-TA2 continued to release Ga steadily throughout the experimentation period (7 d) and exhibited prolonged zinc (Zn) release compared to C-TA0. Interestingly, the Zn release from both GPCs appeared to cause a chemotherapeutic effect against H1092 lung cancer cellsin vitro, with the prolonged Zn release from C-TA2 extending this effect. Unfortunately, both GPCs enhanced the viability of HCC2218 breast cancer cells, suggesting that the chemotherapeutic effects of Zn could be tied to cellular differences in preferred Zn concentrations. The utilization of SAOS-2 and MC3T3 cell lines as bone cell models yielded conflicting results, with the substantial decline in MC3T3 viability closely associated with silicon (Si) release, indicating cellular variations in Si toxicity. Despite this ambiguity, both GPCs exhibited harmful effects on the osteogenesis of primary rat osteoblasts, raising concerns about excessive burst Zn release. While Ga/Zn-doped GPCs hold promise for treating metastatic bone lesions caused by lung cancers, further optimization is required to mitigate cytotoxicity on healthy bone.

Polarimetric second harmonic generation microscopy of partially oriented fibers II: Imaging study.

Polarimetric second harmonic generation (SHG) microscopy imaging is employed to investigate the ultrastructural organization of biological and biomimetic partially oriented fibrillar structures. The linear polarization-in polarization-out SHG microscopy measurements are conducted with rat tail tendon, rabbit cornea, pig cartilage, and biomimetic meso-tetra(4-sulfonatophenyl)porphine (TPPS4) cylindrical aggregates, which represent different two- and three-dimensional (2D and 3D) configurations of C6 symmetry fibril structures in the focal volume (voxel) of the microscope. The polarization-in polarization-out imaging of rat tail tendon reveals that SHG intensity is affected by parallel/antiparallel arrangements of the fibers, and achiral (R) and chiral (C) susceptibility component ratio values change by tilting the tendon fibers out of image plane. The R ratio changes for the 2D crossing fibers observed in cornea tissue. The 3D crossing of fibers also affects R ratio in cartilage tissue. The distinctly different dependence of R on crossing and tilting of fibers is demonstrated in collagen and TPPS4 aggregates, due to the achiral molecular susceptibility ratio having values below and above 3, respectively. The polarimetric microscopy results correspond well with the analytical expressions of amplitude and R and C ratios dependence on the crossing angle of the fibers. The experimentally measured SHG intensity and R and C ratio maps are consistent with the computational modeling of various fiber configurations presented in the preceding article. The demonstrated SHG intensity and R and C ratio dependencies on fibril configurations provide the basis for interpreting polarimetric SHG microscopy images in terms of 3D ultrastructural organization of fibers in each voxel of the samples.

Development and validation of a radiofrequency ablation treatment planning system for vertebral metastases.

PURPOSE: Bone-targeted radiofrequency ablation (RFA) is widely used in the treatment of vertebral metastases. While radiation therapy utilizes established treatment planning systems (TPS) based on multimodal imaging to optimize treatment volumes, current RFA of vertebral metastases has been limited to qualitative image-based assessment of tumour location to direct probe selection and access. This study aimed to design, develop and evaluate a computational patient-specific RFA TPS for vertebral metastases. METHODS: A TPS was developed on the open-source 3D slicer platform, including procedural setup, dose calculation (based on finite element modelling), and analysis/visualization modules. Usability testing was carried out by 7 clinicians involved in the treatment of vertebral metastases on retrospective clinical imaging data using a simplified dose calculation engine. In vivo evaluation was performed in a preclinical porcine model (n = 6 vertebrae). RESULTS: Dose analysis was successfully performed, with generation and display of thermal dose volumes, thermal damage, dose volume histograms and isodose contours. Usability testing showed an overall positive response to the TPS as beneficial to safe and effective RFA. The in vivo porcine study showed good agreement between the manually segmented thermally damaged volumes vs. the damage volumes identified from the TPS (Dice Similarity Coefficient = 0.71 ± 0.03, Hausdorff distance = 1.2 ± 0.1 mm). CONCLUSION: A TPS specifically dedicated to RFA in the bony spine could help account for tissue heterogeneities in both thermal and electrical properties. A TPS would enable visualization of damage volumes in 2D and 3D, assisting clinicians in decisions about potential safety and effectiveness prior to performing RFA in the metastatic spine.

Wide-field Stokes polarimetric microscopy for second harmonic generation imaging.

We employ wide-field second harmonic generation (SHG) microscopy together with nonlinear Stokes polarimetry for quick ultrastructural investigation of large sample areas (700 µm × 700 µm) in thin histology sections. The Stokes vector components for SHG are obtained from the polarimetric measurements with incident and outgoing linear and circular polarization states. The Stokes components are used to construct the images of polarimetric parameters and deduce the maps of ultrastructural parameters of achiral and chiral nonlinear susceptibility tensor components ratios and cylindrical axis orientation in fibrillar materials. The large area imaging was employed for lung tumor margin investigations. The imaging shows reduced SHG intensity, increased achiral susceptibility ratio values, and preferential orientation of collagen strands along the boarder of tumor margin. The wide-field Stokes polarimetric SHG microscopy opens a possibility of quick large area imaging of ultrastructural parameters of tissue collagen, which can be used for nonlinear histopathology investigations.

Establishment and Image based evaluation of a New Preclinical Rat Model of Osteoblastic Bone Metastases.

Bone remodeling is disrupted in the presence of metastases and can present as osteolytic, osteoblastic or a mixture of the two. Established rat models of osteolytic and mixed metastases have been identified changes in structural and tissue-level properties of bone. The aim of this work was to establish a preclinical rat model of osteoblastic metastases and characterize bone quality changes through image-based evaluation. Female athymic rats (n = 22) were inoculated with human breast cancer cells ZR-75-1 and tumor development tracked over 3-4 months with bioluminescence and in-vivo µCT imaging. Bone tissue-level stereological features were quantified on ex-vivo µCT imaging. Histopathology verified the presence of osteoblastic bone. Bone mineral density distribution was assessed via backscattered electron microscopy. Newly formed osteoblastic bone was associated with reduced mineral content and increased heterogeneity leading to an overall degraded bone quality. Characterizing changes in osteoblastic bone properties is relevant to pre-clinical therapeutic testing and treatment planning.

Irregular porous titanium enhances implant stability and bone ingrowth in an intra-articular ovine model.

Two commercially available porous coatings, Gription and Porocoat, were compared for the first time in a challenging intra-articular, weight-bearing, ovine model. Gription has evolved from Porocoat and has higher porosity, coefficient of friction, and microtextured topography, which are expected to enhance bone ingrowth. Cylindrical implants were press-fit into the weight-bearing regions of ovine femoral condyles and bone ingrowth and fixation strength evaluated 4, 8, and 16 weeks postoperatively. Biomechanical push-out tests were performed on lateral femoral condyles (LFCs) to evaluate the strength of the bone-implant interface. Bone ingrowth was assessed in medial femoral condyles (MFCs) as well as implants retrieved from LFCs following biomechanical testing using backscattered electron microscopy and histology. By 16 weeks, Gription-coated implants exhibited higher force (2455 ± 1362 vs. 1002 ± 1466 N; p = 0.046) and stress (12.60 ± 6.99 vs. 5.14 ± 7.53 MPa; p = 0.046) at failure, and trended towards higher stiffness (11,510 ± 7645 vs. 5010 ± 8374 N/mm; p = 0.061) and modulus of elasticity (591 ± 392 vs. 256 ± 431 MPa; p = 0.061). A strong, positive correlation was detected between bone ingrowth in LFC implants and failure force (r = 0.93, p < 10-13 ). By 16 weeks, bone ingrowth in Gription-coated implants in MFCs was 10.50 ± 6.31% compared to 5.88 ± 2.77% in Porocoat (p = 0.095). Observations of the bone-implant interface, made following push-out testing, showed more bony material consistently adhered to Gription compared to Porocoat at all three time points. Gription provided superior fixation strength and bone ingrowth by 16 weeks.

Photodynamic therapy outcome modelling for patients with spinal metastases: a simulation-based study.

Spinal metastases often occur in the advanced stages of breast, lung or prostate cancer, resulting in a significant impact on the patient's quality of life. Current treatment modalities for spinal metastases include both systemic and localized treatments that aim to decrease pain, improve mobility and structural stability, and control tumour growth. With the development of non-toxic photosensitizer drugs, photodynamic therapy (PDT) has shown promise as a minimally invasive non-thermal alternative in oncology, including for spinal metastases. To apply PDT to spinal metastases, predictive algorithms that optimize tumour treatment and minimize the risk of spinal cord damage are needed to assess the feasibility of the treatment and encourage a broad acceptance of PDT in clinical trials. This work presents a framework for PDT modelling and planning, and simulates the feasibility of using a BPD-MA mediated PDT to treat bone metastases at two different wavelengths (690 nm and 565 nm). An open-source software for PDT planning, PDT-SPACE, is used to evaluate different configurations of light diffusers (cut-end and cylindrical) fibres with optimized power allocation in order to minimize the damage to spinal cord or maximize tumour destruction. The work is simulated on three CT images of metastatically involved vertebrae acquired from three patients with spinal metastases secondary to colorectal or lung cancer. Simulation results show that PDT at a 565 nm wavelength has the ability to treat 90% of the metastatic lesion with less than 17% damage to the spinal cord. However, the energy required, and hence treatment time, to achieve this outcome with the 565 nm is infeasible. The energy required and treatment time for the longer wavelength of 690 nm is feasible ([Formula: see text] min), but treatment aimed at 90% of the metastatic lesion would severely damage the proximal spinal cord. PDT-SPACE provides a simulation platform that can be used to optimize PDT delivery in the metastatic spine. While this work serves as a prospective methodology to analyze the feasibility of PDT for tumour ablation in the spine, preclinical studies in an animal model are ongoing to elucidate the spinal cord damage extent as a function of PDT dose, and the resulting short and long term functional impairments. These will be required before there can be any consideration of clinical trials.

Impact of radiofrequency ablation (RFA) on bone quality in a murine model of bone metastases.

Thermal therapies such as radiofrequency ablation (RFA) are gaining widespread clinical adoption in the local treatment of skeletal metastases. RFA has been shown to successfully destroy tumor cells, yet the impact of RFA on the quality of the surrounding bone has not been well characterized. RFA treatment was performed on femora of rats with bone metastases (osteolytic and osteoblastic) and healthy age matched rats. Histopathology, second harmonic generation imaging and backscatter electron imaging were used to characterize changes in the structure, organic and mineral components of the bone after RFA. RFA treatment was shown to be effective in targeting tumor cells and promoting subsequent new bone formation without impacting the surrounding bone negatively. Mineralization profiles of metastatic models were significantly improved post-RFA treatment with respect to mineral content and homogeneity, suggesting a positive impact of RFA treatment on the quality of cancer involved bone. Evaluating the impact of RFA on bone quality is important in directing the growth of this minimally invasive therapeutic approach with respect to fracture risk assessment, patient selection, and multimodal treatment planning.

An Orthotopic Endometrial Cancer Model with Retroperitoneal Lymphadenopathy Made From In Vivo Propagated and Cultured VX2 Cells.

Endometrial cancer is the most common gynecologic malignancy in North America and the incidence is rising worldwide. Treatment consists of surgery with or without adjuvant therapy depending on lymph node involvement as determined by lymphadenectomy. Lymphadenectomy is a morbid procedure, which has not been shown to have a therapeutic benefit in many patients, and thus a new method to diagnose lymph node metastases is required. To test novel imaging agents, a reliable model of endometrial cancer with retroperitoneal lymph node metastases is needed. The VX2 endometrial cancer model has been described frequently in the literature; however, significant variation exists with respect to the method of model establishment. Furthermore, no studies have reported on the use of cultured VX2 cells to create this model as only cells propagated in vivo have been previously used. Herein, we present a standardized surgical method and post-operative monitoring method for the establishment of the VX2 endometrial cancer model and report on the first use of cultured VX2 cells to create this model.

Complex Susceptibilities and Chiroptical Effects of Collagen Measured with Polarimetric Second-Harmonic Generation Microscopy.

Nonlinear optical properties of collagen type-I are investigated in thin tissue sections of pig tendon as a research model using a complete polarimetric second-harmonic generation (P-SHG) microscopy technique called double Stokes-Mueller polarimetry (DSMP). Three complex-valued molecular susceptibility tensor component ratios are extracted. A significant retardance is observed between the chiral susceptibility component and the achiral components, while the achiral components appear to be in phase with each other. The DSMP formalism and microscopy measurements are further used to explain and experimentally validate the conditions required for SHG circular dichroism (SHG-CD) of collagen to occur. The SHG-CD can be observed with the microscope when: (i) the chiral second-order susceptibility tensor component has a non-zero value, (ii) a phase retardance is present between the chiral and achiral components of the second-order susceptibility tensor and (iii) the collagen fibres are tilted out of the image plane. Both positive and negative areas of SHG-CD are observed in microscopy images, which relates to the anti-parallel arrangement of collagen fibres in different fascicles of the tendon. The theoretical formalism and experimental validation of DSMP imaging technique opens new opportunities for ultrastructural characterisation of chiral molecules, in particular collagen, and provides basis for the interpretation of SHG-CD signals. The nonlinear imaging of chiroptical parameters offers new possibilities to further improve the diagnostic sensitivity and/or specificity of nonlinear label-free histopathology.

Elevated Microdamage Spatially Correlates with Stress in Metastatic Vertebrae.

Metastasis of cancer to the spine impacts bone quality. This study aims to characterize vertebral microdamage secondary to metastatic disease considering the pattern of damage and its relationship to stress and strain under load. Osteolytic and mixed osteolytic/osteoblastic vertebral metastases were produced in athymic rats via HeLa cervical or canine Ace-1 prostate cancer cell inoculation, respectively. After 21 days, excised motion segments (T12-L2) were µCT scanned, stained with BaSO4 and re-imaged. T13-L2 motion segments were loaded in axial compression to induce microdamage, re-stained and re-imaged. L1 (loaded) and T12 (unloaded) vertebrae were fixed, sample blocks cut, polished and BSE imaged. µFE models were generated of all L1 vertebrae with displacement boundary conditions applied based on the loaded µCT images. µCT stereological analysis, BSE analysis and µFE derived von Mises stress and principal strains were quantitatively compared (ANOVA), spatial correlations determined and patterns of microdamage assessed qualitatively. BaSO4 identified microdamage was found to be spatially correlated with regions of high stress in µFEA. Load-induced microdamage was shown to be elevated in the presence of osteolytic and mixed metastatic disease, with diffuse, crossed hatched areas of microdamage present in addition to linear microdamage and microfractures in metastatic tissue, suggesting diminished bone quality.

Collagen chirality and three-dimensional orientation studied with polarimetric second-harmonic generation microscopy.

Polarization-dependent second-harmonic generation (P-SHG) microscopy is used to characterize molecular nonlinear optical properties of collagen and determine a three-dimensional (3D) orientation map of collagen fibers within a pig tendon. C6 symmetry is used to determine the nonlinear susceptibility tensor components ratios in the molecular frame of reference χzzz2/χzxx2 and χxyz2/χzxx2 , where the latter is a newly extracted parameter from the P-SHG images and is related to the chiral structure of collagen. The χxyz2/χzxx2 is observed for collagen fibers tilted out of the image plane, and can have positive or negative values, revealing the relative polarity of collagen fibers within the tissue. The P-SHG imaging was performed using a linear polarization-in polarization-out (PIPO) method on thin sections of pig tendon cut at different angles. The nonlinear chiral properties of collagen can be used to construct the 3D organization of collagen in the tissue and determine the orientation-independent molecular susceptibility ratios of collagen fibers in the molecular frame of reference.

The impact of thermal cycling on Staphylococcus aureus biofilm growth on stainless steel and titanium orthopaedic plates.

BACKGROUND: Orthopaedic implant infections are difficult to eradicate because bacteria adhering to implant surfaces inhibit the ability of the immune system and antibiotics to combat these infections. Thermal cycling is a temperature modulation process that improves performance and longevity of materials through molecular structural reorientation, thereby increasing surface uniformity. Thermal cycling may change material surface properties that reduce the ability for bacteria to adhere to the surface of orthopaedic implants. This study aims to determine whether thermal cycling of orthopaedic implants can reduce bacterial growth. METHODS: In a randomized, blinded in-vitro study, titanium and stainless steel plates treated with thermal cycling were compared to controls. Twenty-seven treated and twenty-seven untreated plates were covered with 10 ml tryptic soy broth containing ~ 105 colony forming units (CFU)/ml of bioluminescent Staphylococcus aureus (S. aureus)Xen29 and incubated at 37 °C for 14d. Quantity and viability of bacteria were characterized using bioluminescence imaging, live/dead staining and determination of CFUs. RESULTS: Significantly fewer CFUs grow on treated stainless steel plates compared to controls (p = 0.0088). Similar findings were seen in titanium plates (p = 0.0048) following removal of an outlier. No differences were evident in live/dead staining using confocal microscopy, or in metabolic activity determined using bioluminescence imaging (stainless steel plates: p = 0.70; titanium plates: p = 0.26). CONCLUSION: This study shows a reduction in CFUs formation on thermal cycled plates in-vitro. Further in-vivo studies are necessary to investigate the influence of thermal cycling on bacterial adhesion during bone healing. Thermal cycling has demonstrated improved wear and strength, with reductions in fatigue and load to failure. The added ability to reduce bacterial adhesions demonstrates another potential benefit of thermal cycling in orthopaedics, representing an opportunity to reduce complications following fracture fixation or arthroplasty.

Post-euthanasia micro-computed tomography-based strain analysis is able to represent quasi-static in vivo behavior of whole vertebrae.

Three-dimensional image-based strain measurement in whole bones allows representation of physiological, albeit quasi-static, loading conditions. However, such work to date has been limited to specimens postmortem. The main purpose of this study is to verify the efficacy of deformable image registration of post-euthanasia strain to characterize the in vivo mechanical behavior of rat vertebrae. A micro-computed tomography-compatible custom loading device was used to apply 75 N load to a three-level caudal motion segment of a healthy rat. Loaded and unloaded micro-computed tomography scans were acquired in vivo and post-sacrifice. A micro-computed tomography-based deformable image registration algorithm was used to calculate vertebral strains live and post-euthanasia. No significant difference was found in the in vivo strains (-0.011 ± 0.001) and ex vivo strains (-0.012 ± 0.001) obtained from the comparisons of loaded and unloaded images (p = 0.3). Comparisons between unloaded-unloaded and loaded-loaded scans yielded significantly lower axial strains, representing the error of the method. Qualitatively, high strains were observed adjacent to growth plate regions in evaluating the loaded-unloaded images. Strain patterns in the loaded-loaded and unloaded-unloaded scans were inconsistent as would be expected in representing noise. Overall, live and dead loaded to unloaded comparisons yielded similar strain patterns and magnitudes. Point-wise differences in axial strain fields also supported this observation. This study demonstrated a proof of concept, suggesting that post-euthanasia micro-computed tomography-based strain analysis is able to represent the in vivo quasi-static behavior of rat tail vertebrae.

Dynamic absorption and scattering of water and hydrogel during high-repetition-rate (>100 MHz) burst-mode ultrafast-pulse laser ablation.

High-repetition-rate burst-mode ultrafast-laser ablation and disruption of biological tissues depends on interaction of each pulse with the sample, but under those particular conditions which persist from previous pulses. This work characterizes and compares the dynamics of absorption and scattering of a 133-MHz repetition-rate, burst-mode ultrafast-pulse laser, in agar hydrogel targets and distilled water. The differences in energy partition are quantified, pulse-by-pulse, using a time-resolving integrating-sphere-based device. These measurements reveal that high-repetition-rate burst-mode ultrafast-laser ablation is a highly dynamical process affected by the persistence of ionization, dissipation of plasma plume, neutral material flow, tissue tensile strength, and the hydrodynamic oscillation of cavitation bubbles.

Closure of the annulus fibrosus of the intervertebral disc using a novel suture application device-in vivo porcine and ex vivo biomechanical evaluation.

BACKGROUND CONTEXT: Defects in the annulus fibrosus (AF) remain a challenge in the surgical treatment of lumbar disc herniations with persistent defects, allowing potential re herniation of nucleus pulposus (NP) tissue. A cervical porcine model was chosen to simulate human lumbar intervertebral disc (IVD). PURPOSE: The aim of this study was to determine the technical feasibility of closure of the AF of the IVD using a novel minimally invasive Kerrison-shaped suture application device. STUDY DESIGN: Ex vivo biomechanical and in vivo porcine device evaluations were performed. METHODS: Ex vivo biomechanical evaluation: 15 porcine spinal units were explanted and subjected to mock discectomy. The annular defect was closed using 2-0 non-absorbable (ultra-high molecular-weight polyethylene, UHMWPE) suture and Dines knot. The knot was backed up with two, three, or four throws. The spinal unit was subject to 4000 cycles of flexion/extension with 1500 N of axial load, and assessed for knot slippage. In vivo porcine device evaluation: three pigs (53-57 kg) were anesthetized and underwent a ventral surgical approach to the cervical spine. The AF of two discs was incised, and simulated partial NP discectomy was performed. The defect was closed at one level using the AnchorKnot device to apply the suture with a Dines knot and four throws. The pigs were observed for 4 weeks before euthanasia, allowing 7T magnetic resonance imaging (MRI) and histological evaluation. RESULTS: A Dines knot with four throws experienced no slippage after 4000 cycles. This configuration was tested in vivo. Clinically, the neurological examination in treated pigs was normal following surgery. Histological and MRI assessment confirmed sustained defect closure at 4 weeks. There was no reaction to the suture material and no NP extrusion at any of the sutured levels. CONCLUSIONS: This study demonstrates that it is technically feasible to perform AF defect closure in a porcine model. This novel device achieved AF defect closure that was maintained through 4 weeks in vivo.

µFE models can represent microdamaged regions of healthy and metastatically involved whole vertebrae identified through histology and contrast enhanced µCT imaging.

Micro-damage formation within the skeleton is an important stimulant for bone remodeling, however abnormal build-up of micro-damage can lead to skeletal fragility. In this study, µCT imaging based micro finite element (µFE) models were used to evaluate tissue level damage criteria in whole healthy and metastatically-involved vertebrae. T13-L2 spinal segments were excised from osteolytic (n=3) and healthy (n=3) female athymic rnu/rnu rats. Osteolytic metastasis was generated by intercardiac injection of HeLa cancer cells. Micro-mechanical axial loading was applied to the spinal motion segments under µCT imaging. Vertebral samples underwent BaSO4 staining and sequential calcein/fuchsin staining to identify load induced micro-damage. µCT imaging was used generate specimen specific µFE models of the healthy and osteolytic whole rat vertebrae. Model boundary conditions were generated through deformable image registration of loaded and unloaded scans. Elevated stresses and strains were detected in regions of micro-damage identified through histological and BaSO4 staining within healthy and osteolytic vertebral models, as compared to undamaged regions. Additionally, damaged regions of metastatic vertebrae experienced significantly higher local stresses and strains than those in the damaged regions of healthy specimens. Areas identified by BaSO4 staining, however, yielded lower levels of stress and strain in damaged and undamaged regions of healthy and metastatic vertebrae as compared to fuschin staining. The multimodal (experimental, image-based and computational) techniques used in this study demonstrated the ability of local stresses and strains computed through µFE analysis to identify trabecular micro-damage, that can be applied to biomechanical analyses of healthy and diseased whole bones.

Phototheranostic Porphyrin Nanoparticles Enable Visualization and Targeted Treatment of Head and Neck Cancer in Clinically Relevant Models.

Head and neck cancer is the fifth most common type of cancer worldwide and remains challenging for effective treatment due to the proximity to critical anatomical structures in the head and neck region, which increases the probability of toxicity from surgery and radiotherapy, and therefore emphasizes the importance of maximizing the targeted ablation. We have assessed the effectiveness of porphysome nanoparticles to enhance fluorescence and photoacoustic imaging of head and neck tumors in rabbit and hamster models. In addition, we evaluated the effectiveness of this agent for localized photothermal ablative therapy of head and neck tumors. We have demonstrated that porphysomes not only enabled fluorescence and photoacoustic imaging of buccal and tongue carcinomas, but also allowed for complete targeted ablation of these tumors. The supremacy of porphysome-enabled photothermal therapy over surgery to completely eradicate primary tumors and metastatic regional lymph node while sparing the adjacent critical structures' function has been demonstrated for the first time. This study represents a novel breakthrough that has the potential to revolutionize our approach to tumor diagnosis and treatment in head and neck cancer and beyond.

A multimodal nano agent for image-guided cancer surgery.

Intraoperative imaging technologies including computed tomography and fluorescence optical imaging are becoming routine tools in the cancer surgery operating room. They constitute an enabling platform for high performance surgical resections that assure local control while minimizing morbidity. New contrast agents that can increase the sensitivity and visualization power of existing intraoperative imaging techniques will further enhance their clinical benefit. We report here the development, detection and visualization of a dual-modality computed tomography and near-infrared fluorescence nano liposomal agent (CF800) in multiple preclinical animal models of cancer. We describe the successful application of this agent for combined preoperative computed tomography based three-dimensional surgical planning and intraoperative target mapping (>200 Hounsfield Units enhancement), as well as near-infrared fluorescence guided resection (>5-fold tumor-to-background ratio). These results strongly support the clinical advancement of this agent for image-guided surgery with potential to improve lesion localization, margin delineation and metastatic lymph node detection.

Helical coil electrode radiofrequency ablation designed for application in osteolytic vertebral tumors--initial evaluation in a porcine model.

BACKGROUND CONTEXT: Radiofrequency ablation (RFA) is emerging as a complementary treatment for vertebral metastases. Traditional RFA induces frictional heating leading to local tissue necrosis but often yields small, incomplete, and inhomogeneous zones of ablation in bone. We have developed a new bone-specific RFA electrode that uses a nontraditional frequency (27.12 MHz) and geometry (helical), exploiting a magnetic field and an electric field to generate larger and more comprehensive treatment zones. PURPOSE: The purpose of the study was to evaluate the feasibility and safety of the Bone Coil RFA electrode in the spine. STUDY DESIGN: This is a preclinical in vivo study based on basic science. METHODS: Under institutional approval, six healthy Yorkshire pigs received a sham and an RF treatment in two adjacent cervical vertebrae. To deploy the Bone Coil RFA device in dense porcine vertebrae, a surgical approach was required; an irrigated coring drill bit created a cylindrical path in the vertebral bodies through which the RFA electrodes were placed. The electronic circuit was completed by four grounding pads. Treatment was delivered for 10 minutes at 20 W (n=1), 25 W (n=1), and 30 W (n=4). To monitor the thermal rise and for safety, fiber-optic probes recorded temperatures in the center of each coil and near the spinal foramen. After the procedure, animals were monitored for 2 weeks. Magnetic resonance imaging (MRI) was completed immediately after treatment and at 14 days. Magnetic resonance image segmentation and histology were used to evaluate the ablation volume. RESULTS: Comprehensive treatment of the porcine vertebrae was demonstrated by temperature monitoring, MRI, and histology. Large zones of RF ablation were obtained (RF: 3.72±0.73 cm3 vs. sham: 1.98±0.16 cm3, p<.05), confined within the vertebral body. Internal temperatures were elevated with RF (66.1 °C-102.9 °C), without temperature rise outside of the vertebrae (38.2 °C ± 1.5 °C). Mobility, neurological responses, and behavior were normal, consistent with preprocedural examination. Magnetic resonance imaging best visualized ablation at Day 14. Histology revealed comprehensive homogeneous coagulative necrosis with little peripheral sign of repair. CONCLUSIONS: The Bone Coil RFA device created large intravertebral ablation volumes with no neurologic sequelae. Radiofrequency thermal ablation (clearly distinguished from the much smaller effects arising from core drilling) corresponded to the homogeneous necrosis visible on histology.