Chun-g R. Chen

Optimizing Electrode Placement Using Finite-Element Models in Radiofrequency Ablation Treatment Planning

Conventional radiofrequency ablation (RFA) planning methods for identifying suitable electrode placements typically use geometric shapes to model ablation outcomes. A method is presented for searching electrode placements that couples finite-element models (FEMs) of RFA together with a novel optimization strategy. The method was designed to reduce the need for model solutions per local search step. The optimization strategy was tested against scenarios requiring single and multiple ablations. In particular, for a scenario requiring multiple ablations, a domain decomposition strategy was described to minimize the complexity of simultaneously searching multiple electrode placements. The effects of nearby vasculature on optimal electrode placement were also studied. Compared with geometric planning approaches, FEMs could potentially deliver electrode placement plans that provide more physically meaningful predictions of therapeutic outcomes.

A prototype ultrasound-guided laparoscopic radiofrequency ablation system

BackgroundAdvanced laparoscopic procedures, particularly laparoscopic liver resection and ablation, may benefit from image-guided surgery techniques that involve interactive three-dimensional imaging and instrument tracking.MethodsA prototype system for laparoscopic ultrasound-guided radiofrequency ablation was designed and implemented. This system uses an infrared camera to track instruments and runs on a personal computer. Features of the system include spatially registered ultrasound visualization, volume reconstruction, and interactive targeting. Targeting of accuracy studies was performed by directing a tracked needle to a phantom target.ResultsUltrasound data collection and volume reconstruction can be achieved within minutes and interactively reviewed by the surgeon. Early results with phantom experiments demonstrate a targeting accuracy of 5 to 10 mm.ConclusionsThese results support the further development of this and similar image-guided surgery systems for specific laparoscopic procedures. Eventually, rigorous clinical evaluation will be necessary to prove their value.

Model-Updated Image Guidance: A Statistical Approach to Gravity-Induced Brain Shift.

Compensating for intraoperative brain shift using computational models has been used with promising results. Since computational time is an important factor during neurosurgery, a prior knowledge of a patients orientation and changes in tissue buoyancy force would be valuable information to aid in predicting shift due to gravitational forces. Since the latter is difficult to quantify intraoperatively, a statistical model for predicting intraoperative brain deformations due to gravity is reported. This statistical model builds on a computational model developed earlier. For a given set of patients orientation and amount of CSF drainage, the intraoperative brain shift is calculated using the computational model. These displacements are then validated against measured displacements to predict the intraoperative brain shift. Though initial results are promising, further study is needed before the statistical model can be used for model-updated image-guided surgery.

CD47 blockade reduces ischemia-reperfusion injury and improves outcomes in a rat kidney transplant model.

Background Ischemia-reperfusion injury (IRI) significantly contributes to delayed graft function and inflammation, leading to graft loss. Ischemia-reperfusion injury is exacerbated by the thrombospondin-1-CD47 system through inhibition of nitric oxide signaling. We postulate that CD47 blockade and prevention of nitric oxide inhibition reduce IRI in organ transplantation. Methods We used a syngeneic rat renal transplantation model of IRI with bilaterally nephrectomized recipients to evaluate the effect of a CD47 monoclonal antibody (CD47mAb) on IRI. Donor kidneys were flushed with CD47mAb OX101 or an isotype-matched control immunoglobulin and stored at 4°C in University of Wisconsin solution for 6 hr before transplantation. Results CD47mAb perfusion of donor kidneys resulted in marked improvement in posttransplant survival, lower levels of serum creatinine, blood urea nitrogen, phosphorus and magnesium, and less histological evidence of injury. In contrast, control groups did not survive more than 5 days, had increased biochemical indicators of renal injury, and exhibited severe pathological injury with tubular atrophy and necrosis. Recipients of CD47mAb-treated kidneys showed decreased levels of plasma biomarkers of renal injury including Cystatin C, Osteopontin, Tissue Inhibitor of Metalloproteinases-1 (TIMP1), &bgr;2-Microglobulin, Vascular Endothelial Growth Factor A (VEGF-A), and clusterin compared to the control group. Furthermore, laser Doppler assessment showed higher renal blood flow in the CD47mAb-treated kidneys. Conclusion These results provide strong evidence for the use of CD47 antibody–mediated blockade to reduce IRI and improve organ preservation for renal transplantation.

Optimizing needle placement in treatment planning of radiofrequency ablation

A computational method is presented for optimizing needle placement in radiofrequency ablation treatment planning. The parameterized search is guided by an objective function that depends on transient, finite element solutions of coupled thermal and potential equations for each needle placement. A framework is introduced for solving the electrostatic equation by using boundary elements to model the needle as discrete current sources embedded within a finite element mesh. This method permits finite element solutions for multiple needle placements without remeshing. We demonstrate that the method produces a search space amenable to gradient-based optimization techniques.

Characterization of tracked radiofrequency ablation in phantom

In radiofrequency ablation (RFA), successful therapy requires accurate, image-guided placement of the ablation device in a location selected by a predictive treatment plan. Current planning methods rely on geometric models of ablations that are not sensitive to underlying physical processes in RFA. Implementing plans based on computational models of RFA with image-guided techniques, however, has not been well characterized. To study the use of computational models of RFA in planning needle placement, this work compared ablations performed with an optically tracked RFA device with corresponding models of the ablations. The calibration of the tracked device allowed the positions of distal features of the device, particularly the tips of the needle electrodes, to be determined to within 1.4±0.6mm of uncertainty. Ablations were then performed using the tracked device in a phantom system based on an agarose-albumin mixture. Images of the sliced phantom obtained from the ablation experiments were then compared with the predictions of a bioheat transfer model of RFA, which used the positional data of the tracked device obtained during ablation. The model was demonstrated to predict 90% of imaged pixels classified as being ablated. The discrepancies between model predictions and observations were analyzed and attributed to needle tracking inaccuracy as well as to uncertainties in model parameters. The results suggest the feasibility of using finite element modeling to plan ablations with predictable outcomes when implemented using tracked RFA.

High-speed photoacoustic microscopy of mouse cortical microhemodynamics

We applied high-speed photoacoustic microscopy (PAM) for both cortical microenvironment studies and dynamic brain studies, with micrometer-level optical resolution and a millisecond-level cross-sectional imaging speed over a millimeter-level field of view. We monitored blood flow redistribution in mini-stroke mouse models and cerebral autoregulation induced by a vasoactive agent. Our results collectively suggest that high-speed PAM is a promising tool for understanding dynamic neurophysiological phenomena, complementing conventional imaging modalities.

Ultrasound-guided ablation system for laparoscopic liver surgery

This work describes the design and implementation of a system for liver tumor ablation guided by ultrasound. Features of the system include spatially registered ultrasound visualization, ultrasound volume reconstruction, and interactive targeting. Early results with phantom experiments indicate a targeting accuracy of 5-10mm. The system serves as a foundation for further clinical studies and applications of image-guided therapy to liver procedures.

TH‐AB‐304‐03: Tumor Control Probability Applied to Lung Cancer: A Statistical Test of the Independence of Voxel Response

Purpose: Conventional radiotherapy planning uses simplified DVH-derived metrics (e.g. D99, D95) as surrogates for tumor control probability when evaluating plan quality. While this has the advantage of providing an easily derived predictor variable, such metrics fail to consider critical aspects of the underlying radiobiology. Counter to observed radiobiological effects, there is a prevailing assumption of tumor subvolume independence. We tested this by introducing a parameter to capture departures from independence using a modified metric, termed the “generalized tumor dose” (gTD). Methods: For given dose distributions, cell survival was derived from a comprehensive biological model (Jeong, 2013 Phys. Med. Biol.). The gTD metric applied a generalized mean term, q, to subvolume survival values, with this term optimized according to its predictive power over the NSCLS cohort (N=316). Patients were treated 1.8–2.2 Gy/Fx in 28–39 Fxs (n=50), or 2.75 Gy/Fx in 24 fractions (n=266). Results were compared to other metrics according binary outcome and actuarial survival prediction. Results: Fitting model parameters to combined cohort data using log-likelihood and actuarial methods, we derived an optimized generalized mean parameter q of −1.14 (95% confidence interval upper bound=0.08). Patient-specific gTD values derived using this value showed superior performance to other clinical metrics. For gTD, normalized log-likelihood=−0.471, AUC=0.634, and R^2=0.066, versus normalized log-likelihood=−0.508/−0.504, AUC=0.473/0.462, and R^2=0.0011/0.0014 for D99/D95. Furthermore, when q wasn’t incorporated into the model (q=1, implicitly), AUC decreased to 0.622, normalized log-likelihood to −0.501 and R^2 to 0.0144. Conclusion: Negative q values suggest areas of highest dose play a greater role in determining outcome than expected based only on TCP.The biological origin of this effect could be of several potential causes, including bystander effects, genomic intra-tumor heterogeneity, or tumor shrinkage. Accounting for these interactions, the gTD metric provides superior accuracy as a predictor of outcome.

Intraoperative Visualization of Hepatocellular Carcinoma with Indocyanine Green: Revealing the Mechanisms behind the Glowing Tumor

Reliable intraoperative detection of tumors is important in the surgical management of malignant disease. In hepatocellular carcinoma (HCC), for instance, it is well known that failure to achieve R0 resections results in recurrence and reduced survival. Beyond the tactile and visual senses of the surgeon, additional tools are needed to reveal the extent of tumors and their involvement with nearby anatomy in order to achieve safe, curative resections. However, the technologies used to provide such anatomical and functional information for guiding resections have not changed considerably over the years and are based largely on conventional imaging modalities used preoperatively. Of these, intraoperative ultrasound (IOUS) remains the most common form of imaging available to visualize intra-abdominal tumors, although other modalities like intraoperative magnetic resonance and computed tomography have been tried in neurosurgery. To exploit fully the pre-operative advantages of these modalities inside the operating room, many scientific, engineering, and logistical challenges remain to be solved. One problem is that these imaging systems typically discriminate malignant from benign tissues on the basis of their physical properties (e.g. density, vascular flow, etc.) and generally not on their actual biology (e.g. tumor-specific proteins, genetic mutations, etc.). Another problem is that the images seen on a two-dimensional monitor are presented without the three-dimensional context of the actual patient and must be reoriented back in the operative field in order to be useful. Although systems exist to map pre-operative scans onto the intra-operative scene, these technologies are still being evaluated. Without addressing these problems, such images would only serve to suggest a possible tumor in a possible location, requiring the surgeon to explore and sample the tissue to confirm a tumor. In this issue, Ishizawa et al. have explored the use of indocyanine green (ICG) in vivo to make HCCs fluorescent for direct visualization intraoperatively. Unlike the imaging methods described above, the authors demonstrate that the tumor retention of ICG is based, in part, on its biology and that the tumor fluorescence is directly visible intraoperatively in nearly every patient of a fairly large series. As a historical note, ICG was first described in liver surgery, not as a tumor marker but as a means of assessing peri-operative liver function via the clearance of the marker by the organ. ICG rapidly binds albumin upon administration and is then transported to the liver, where it is excreted into the biliary system. Later, ICG was also shown to fluoresce in the near-infrared (NIR) wavelength and was often used as an indicator dye in angiography. This fluorescent property makes ICG and other similar dyes attractive for intra-operative use because its detection is not based on ionizing radiation. Furthermore, at the wavelength at which ICG is excited, the surrounding tissues do not contribute to background auto-fluorescence, allowing ICG to be detected with a high signal-to-noise ratio. Another property of ICG that engendered its clinical use is that it is relatively non-toxic, with few side effects, although the application of ICG as an imaging agent is still considered off-label use. It was against this historical backdrop that the preferential retention of ICG in HCC was accidentally discovered. Nevertheless, the mechanism by which this retention occurred remains unknown. It was hypothesized that ICG retention was a product of disruption in biliary excretion and from leaky portal vasculature near the tumor. Despite these uncertainties, multiple applications of ICG in oncologic surgeries have since been reported. Society of Surgical Oncology 2013Reliable intraoperative detection of tumors is important in the surgical management of malignant disease. In hepatocellular carcinoma (HCC), for instance, it is well known that failure to achieve R0 resections results in recurrence and reduced survival. Beyond the tactile and visual senses of the surgeon, additional tools are needed to reveal the extent of tumors and their involvement with nearby anatomy in order to achieve safe, curative resections. However, the technologies used to provide such anatomical and functional information for guiding resections have not changed considerably over the years and are based largely on conventional imaging modalities used preoperatively. Of these, intraoperative ultrasound (IOUS) remains the most common form of imaging available to visualize intra-abdominal tumors, although other modalities like intraoperative magnetic resonance and computed tomography have been tried in neurosurgery. To exploit fully the pre-operative advantages of these modalities inside the operating room, many scientific, engineering, and logistical challenges remain to be solved. One problem is that these imaging systems typically discriminate malignant from benign tissues on the basis of their physical properties (e.g. density, vascular flow, etc.) and generally not on their actual biology (e.g. tumor-specific proteins, genetic mutations, etc.). Another problem is that the images seen on a two-dimensional monitor are presented without the three-dimensional context of the actual patient and must be reoriented back in the operative field in order to be useful. Although systems exist to map pre-operative scans onto the intra-operative scene, these technologies are still being evaluated. Without addressing these problems, such images would only serve to suggest a possible tumor in a possible location, requiring the surgeon to explore and sample the tissue to confirm a tumor. In this issue, Ishizawa et al. have explored the use of indocyanine green (ICG) in vivo to make HCCs fluorescent for direct visualization intraoperatively. Unlike the imaging methods described above, the authors demonstrate that the tumor retention of ICG is based, in part, on its biology and that the tumor fluorescence is directly visible intraoperatively in nearly every patient of a fairly large series. As a historical note, ICG was first described in liver surgery, not as a tumor marker but as a means of assessing peri-operative liver function via the clearance of the marker by the organ. ICG rapidly binds albumin upon administration and is then transported to the liver, where it is excreted into the biliary system. Later, ICG was also shown to fluoresce in the near-infrared (NIR) wavelength and was often used as an indicator dye in angiography. This fluorescent property makes ICG and other similar dyes attractive for intra-operative use because its detection is not based on ionizing radiation. Furthermore, at the wavelength at which ICG is excited, the surrounding tissues do not contribute to background auto-fluorescence, allowing ICG to be detected with a high signal-to-noise ratio. Another property of ICG that engendered its clinical use is that it is relatively non-toxic, with few side effects, although the application of ICG as an imaging agent is still considered off-label use. It was against this historical backdrop that the preferential retention of ICG in HCC was accidentally discovered. Nevertheless, the mechanism by which this retention occurred remains unknown. It was hypothesized that ICG retention was a product of disruption in biliary excretion and from leaky portal vasculature near the tumor. Despite these uncertainties, multiple applications of ICG in oncologic surgeries have since been reported. Society of Surgical Oncology 2013