Fabrication of Molecular Blocks with High Responsiveness to the Cancer Microenvironment by Ursodeoxycholic Acid.

In cancer therapy, a drug delivery system (DDS) has been widely studied to achieve selective drug accumulation at the tumor site. However, DDS still has a major drawback in that it requires multistep processes for intracellular delivery, resulting in low efficiency of drug delivery. To overcome this problem, we recently reported a molecular block (MB) that disrupts cancer cell membranes in the cancer microenvironment using deoxycholic acid (DCA). However, the MB showed considerable cytotoxicity even at neutral pH, possibly due to the structural hydrophobic property of DCA. Herein, we focused on selecting the most suitable bile acid for an MB that possessed high responsiveness to the cancer microenvironment without cytotoxicity at neutral pH. Cell viabilities of the free bile acids such as DCA, chenodeoxycholic acid (CDCA), cholic acid (CA), and ursodeoxycholic acid (UDCA) were evaluated at neutral pH (pH = 7.4) and a cancer acidic environment (pH = 6.3-6.5). The half-maximal inhibition concentration (IC50) value of UDCA at pH = 7.4 showed an approximately 7.5-fold higher IC50 value than that at pH = 6.3, whereas the other bile acids yielded less than a 4-fold IC50 value difference between the same pHs. Biocompatible poly(vinyl alcohol) (PVA) was functionalized with UDCA (PVA-UDCA) for the synthesis of higher responsiveness to the cancer microenvironment without cytotoxicity at neutral pH. Importantly, 56% pancreatic cancer cell death was observed at pH = 6.5, whereas only 10% was detected at neutral pH by the PVA-UDCA treatment. However, PVA-DCA indicated almost the same cancer cell death property, independent of pH conditions. These results suggest PVA-UDCA shows great potential for a new class of MB.

Fabrication of a Polymeric Inhibitor of Proximal Metabolic Enzymes in Hypoxia for Synergistic Inhibition of Cancer Cell Proliferation, Survival, and Migration.

Since conventional molecular targeted drugs often result in side effects, the development of novel molecular targeted drugs with both high efficacy and selectivity is desired. Simultaneous inhibition of metabolically and spatiotemporally related proteins/enzymes is a promising strategy for improving therapeutic interventions in cancer treatment. Herein, we report a poly-α-l-glutamate-based polymer inhibitor that simultaneously targets proximal transmembrane enzymes under hypoxia, namely, carbonic anhydrase IX (CAIX) and zinc-dependent metalloproteinases. A polymer incorporating two types of inhibitors more effectively inhibited the proliferation and migration of human breast cancer cells than a combination of two polymers functionalized exclusively with either inhibitor. Synergistic inhibition of cancer cells would occur owing to the hetero-multivalent interactions of the polymer with proximate enzymes on the cancer cell membrane. Our results highlight the potential of polymer-based cancer therapeutics.

Development of Highly Sensitive Molecular Blocks at Cancer Microenvironment for Rapid Cancer Cell Death.

Improving the efficiency and selectivity of drug delivery systems (DDS) is still a major challenge in cancer therapy. Recently, the low transport efficiency of anticancer drugs using a nanocarrier due to the elimination of the carriers from the blood circulation and the blocking by tumor stromal tissues surrounding cancer cells has been reported. Furthermore, multiple steps are required for their intracellular delivery. We recently reported a cancer microenvironment-targeting therapy termed molecular block (MB) which induced cancer cell death by a pH-driven self-aggregation and cell membrane disruption at tumor microenvironment. The MB were designed to disperse as nanoscale assemblies in the bloodstream for efficient circulation and penetration through the stromal tissues. When the MBs reach the tumor site, they self-assembled in microscale aggregates on the cancer cell surfaces in response to the cancer microenvironment and induced cancer cell death. However, in vivo study in mice showed that the MB could not efficiently accumulate at the tumor site because slight hydrophobic aggregations in the bloodstream might potentially be the reason for the off-target accumulation. In this study, we optimize the hydrophilic-hydrophobic balance of MB for avoiding the off-target accumulation and for gaining higher sensitivity to the cancer microenvironment at weak acid condition. Copper-free click reaction with propiolic acid was used to reduce the hydrophobicity of the main chain and obtain higher responsive MB at cancer microenvironment for rapid cell killing. The optimized MB can be considered as a promising approach for an improved cancer cell targeting.

Affinity purification of multifunctional oligomeric ligands synthesized via controlled radical polymerization.

Abiotic oligomeric ligands with a strong affinity for a target peptide sequence were isolated by affinity purification from a pool of 30-mer acrylic random ter-oligomers that were synthesized via a controlled radical polymerization process. Our results indicate that the oligomeric ligands with suitable sequence and/or stereochemical configurations for the target can be isolated from as-polymerized random co-polymers based on the affinity to the target. This process will be a powerful tool for the development of stable and inexpensive ligands that can be used to detect, neutralize and purify proteins with a target epitope sequence.

Engineering the Binding Kinetics of Synthetic Polymer Nanoparticles for siRNA Delivery.

The affinity of a synthetic polymer nanoparticle (NP) to a target biomacromolecule is determined by the association and dissociation rate constants (kon, koff) of the interaction. The individual rates and their sensitivity to local environmental influences are important factors for the on-demand capture and release a target biomacromolecule. Positively charged NPs for small interfering RNA (siRNA) delivery is a case in point. The knockdown efficacy of siRNA can be strongly influenced by the binding kinetics to the NP. Here, we show that kon and koff of siRNA to NPs can be individually engineered by tuning the chemical structure and composition of the NP. N-Isopropylacrylamide-based NPs functionalized with hydrophobic and amine monomers were used. koff decreased by increasing the amount of amine groups in the NP, whereas kon did not change. Importantly, NPs showing a low koff at pH 5.5 together with a high koff at pH 7.4 showed high knockdown efficiency when NP/siRNA complexes were packaged in lipid nanoparticles. These results provide direct evidence for the premise that the efficacy of an siRNA delivery vector is linked with the strong affinity to the siRNA in the endosome and low affinity in the cytoplasm.

CT-based automated planning of acetabular cup for total hip arthroplasty (THA) based on hybrid use of two statistical atlases.

PURPOSE: This study describes the use of CT images in atlas-based automated planning methods for acetabular cup implants in total hip arthroplasty (THA). The objective of this study is to develop an automated cup planning method considering the statistical distribution of the residual thickness. METHODS: From a number of past THA planning datasets, we construct two statistical atlases that represent the surgeon's expertise. The first atlas is a pelvis-cup merged statistical shape model (PC-SSM), which encodes global spatial relationships between the patient anatomy and implant. The other is a statistical residual thickness map (SRTM) of the implant surface, which encodes local spatial constraints of the anatomy and implant. In addition to PC-SSM and SRTM, we utilized the minimum thickness as a threshold constraint to prevent penetration. RESULTS: The proposed method was applied to the pelvis shapes segmented from CT images of 37 datasets of osteoarthritis patients. Automated planning results with manual segmentation were compared to the plans prepared by an experienced surgeon. There was no significant difference in the average cup size error between the two methods (1.1 and 1.2 mm, respectively). The average positional error obtained by the proposed method, which integrates the two atlases, was significantly smaller (3.2 mm) than the previous method, which uses single atlas (3.9 mm). In the proposed method with automated segmentation, the size error of the proposed method for automated segmentation was comparable (1.1 mm) to that for manual segmentation (1.1 mm). The average positional error was significantly worse (4.2 mm) than that using manual segmentation (3.2 mm). If we only consider mildly diseased cases, however, there was no significance between them (3.2 mm in automated and 2.6 mm in manual segmentation). CONCLUSION: We infer that integrating PC-SSM and SRTM is a useful approach for modeling experienced surgeon's preference during cup planning.

Morphological analysis of the effects of intraoperative transrectal compression of the prostate during high-intensity focused ultrasound for localized prostate cancer.

OBJECTIVES: To evaluate the effects of transrectal compression of the prostate for intra-operative prostatic swelling and intraprostatic point shift during high-intensity focused ultrasound treatment of localized prostate cancer. METHODS: Patients treated with whole-gland high-intensity focused ultrasound as primary monotherapy for localized prostate cancer were enrolled in the study. Using the standard and compression method, the volumes of degassed water in the balloon covering the high-intensity focused ultrasound probe were 50 mL and 80-160 mL, respectively. To identify prostatic swelling and shift during high-intensity focused ultrasound and the volume occupied by the non-enhanced area, three-dimensional prostate models were reconstructed using ultrasound and contrast-enhanced magnetic resonance imaging. RESULTS: In comparison with the standard (n = 40) and compression (n = 48) methods, intraoperative increase in the prostate volume (21% vs 5.3%; P = 0.044), intraprostatic point shift (4 mm vs 2 mm, P = 0.040 in the transition zone; 3 mm vs 0 mm; P = 0.001 in the peripheral zone) and the volume occupied by the non-enhanced area (89% vs 96%; P = 0.001) were significantly suppressed. The biochemical disease-free survival rate in patients treated using the compression method was significantly improved relative to the standard method (92.6% vs 76.5%; P = 0.038). Regarding complications, there was no significant difference in the rate of urethral stricture (P = 0.9), urinary tract infection (P = 0.9), incontinence (P = 0.3), erectile dysfunction (P = 0.9) or recto-urethral fistula between the patients treated using the standard and compression methods. CONCLUSIONS: Intraoperative transrectal compression suppresses intraoperative increase in the prostate volume and intraprostatic point shift during high-intensity focused ultrasound, having the potential to achieve precise whole-gland and lesion-targeted focal therapy.

Three-dimensional navigation system integrating position-tracking technology with a movable tablet display for percutaneous targeting.

OBJECTIVES: To assess the feasibility of a novel percutaneous navigation system (Translucent Medical, Inc., Santa Cruz, CA, USA) that integrates position-tracking technology with a movable tablet display. MATERIALS AND METHODS: A total of 18 fiducial markers, which served as the target centres for the virtual tumours (target fiducials), were implanted in the prostate and kidney of a fresh cadaver, and preoperative computed tomography (CT) was performed to allow three-dimensional model reconstruction of the surgical regions, which were registered on the body intra-operatively. The position of the movable tablet's display could be selected to obtain the best recognition of the interior anatomy. The system was used to navigate the puncture needle (with position-tracking sensor attached) using a colour-coded, predictive puncture-line. When the operator punctured the target fiducial, another fiducial, serving as the centre of the ablative treatment (treatment fiducial), was placed. Postoperative CT was performed to assess the digitized distance (representing the real distance) between the target and treatment fiducials to evaluate the accuracy of the procedure. RESULTS: The movable tablet display, with position-tracking sensor attached, enabled the surgeon to visualize the three-dimensional anatomy of the internal organs with the help of an overlaid puncture line for the puncture needle, which also had a position-tracking sensor attached. The mean (virtual) distance from the needle tip to the target (calculated using the computer workstation), was 2.5 mm. In an analysis of each digitalized axial component, the errors were significantly greater along the z-axis (P < 0.01), suggesting that the errors were caused by organ shift or deformation. CONCLUSION: This virtual navigation system, integrating a position-tracking sensor with a movable tablet display, is a promising advancement for facilitating percutaneous interventions. The movable display over the patient shows a preoperative three-dimensional image that is aligned to the patient. Moving the display moves the image, creating the feeling of looking through a window into the patient, resulting in instant perception and a direct, intuitive connection between the physician and the anatomy.

Time-dependent change of blood flow in the prostate treated with high-intensity focused ultrasound.

Avascular areas on contrast-enhanced magnetic resonance imaging have been considered to be areas of localized prostate cancer successfully treated by high-intensity focused ultrasound. However, the optimal timing of magnetic resonance imaging has not been discussed. The thermal effect of high-intensity focused ultrasound is degraded by regional prostatic blood flow. Conversely, the mechanical effect of high-intensity focused ultrasound (cavitation) is not affected by blood flow, and can induce vessel damage. In this series, the longitudinal change of blood flow on contrast-enhanced magnetic resonance imaging was observed from postoperative day 1 to postoperative day 14 in 10 patients treated with high-intensity focused ultrasound. The median rates of increase in the non-enhanced volume of the whole gland, transition zone and peripheral zone from postoperative day 1 to postoperative day 14 were 36%, 39%, and 34%, respectively. In another pathological analysis of the prostate tissue of 17 patients immediately after high-intensity focused ultrasound without neoadjuvant hormonal therapy, we observed diffuse coagulative degeneration and partial non-coagulative prostate tissue around arteries with vascular endothelial cell detachment. These observations on contrast-enhanced magnetic resonance imaging support a time-dependent change of the blood flow in the prostate treated with high-intensity focused ultrasound. Additionally, our pathological findings support the longitudinal changes of these magnetic resonance imaging findings. Further large-scale studies will investigate the most appropriate timing of contrast-enhanced magnetic resonance imaging for evaluation of the effectiveness of high-intensity focused ultrasound for localized prostate cancer.

Three-dimensional surgical navigation model with TilePro display during robot-assisted radical prostatectomy.

Abstract To facilitate robotic nerve-sparing radical prostatectomy, we developed a novel three-dimensional (3D) surgical navigation model that is displayed on the TilePro function of the da Vinci® surgeon console. Based on 3D transrectal ultrasonography (TRUS)-guided prostate biopsies, we reconstructed a 3D model of the TRUS-visible, histologically confirmed "index" cancer lesion in 10 consecutive patients. Five key anatomic structures (prostate, image-visible biopsy-proven "index" cancer lesion, neurovascular bundles, urethra, and recorded biopsy trajectories) were image-fused and displayed onto the TilePro function of the robotic console. The 3D model facilitated careful surgical dissection in the vicinity of the biopsy-proven index lesion. Geographic location of the index lesion on the final histology report correlated with the software-created 3D model. Negative surgical margins were achieved in 90%, except for one case with extensive extra-prostate extension. At postoperative 3 months, prostate-specific antigen levels were undetectable (<0.03 ng/mL) in all cases. The initial experience of the navigation model is presented.

Prostate swelling and shift during high intensity focused ultrasound: implication for targeted focal therapy.

PURPOSE: We quantified prostate swelling and the intraprostatic point shift during high intensity focused ultrasound using real-time ultrasound. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Whole gland high intensity focused ultrasound was done in 44 patients with clinically localized prostate cancer. Three high intensity focused ultrasound sessions were required to cover the entire prostate, including the anterior zone (session 1), middle zone (session 2) and posterior zone (session 3). Computer assisted 3-dimensional reconstructions based on 3 mm step-section images of intraoperative transrectal ultrasound were compared before and after each session. RESULTS: Most prostate swelling and intraprostatic point shifts occurred during session 1. The median percent volume increase was 18% for the transition zone, 9% for the peripheral zone and 13% for the entire prostate. The volume percent increase in the transition zone (p <0.001), peripheral zone (p = 0.001) and entire prostate (p = 0.001) statistically depended on the volume of each area measured preoperatively. The median 3-dimensional intraprostatic shift was 3.7 mm (range 0.9 to 13) in the transition zone and 5.5 mm (range 0.2 to 14) in the peripheral zone. A significant negative linear correlation was found between the preoperative presumed circle area ratio, and the percent increase in prostate volume (p = 0.001) and shift (p = 0.01) during high intensity focused ultrasound. CONCLUSIONS: We quantified significant prostate swelling and shift during high intensity focused ultrasound. Smaller prostates and a smaller preoperative presumed circle area ratio were associated with greater prostate swelling and intraprostatic shifts. Real-time intraoperative adjustment of the treatment plan impacts the achievement of precise targeting during high intensity focused ultrasound, especially in prostates with a smaller volume and/or a smaller preoperative presumed circle area ratio.

Zero ischemia anatomical partial nephrectomy: a novel approach.

PURPOSE: We present a novel concept of zero ischemia anatomical robotic and laparoscopic partial nephrectomy. MATERIALS AND METHODS: Our technique primarily involves anatomical vascular microdissection and preemptive control of tumor specific, tertiary or higher order renal arterial branch(es) using neurosurgical aneurysm micro-bulldog clamps. In 58 consecutive patients the majority (70%) had anatomically complex tumors including central (67%), hilar (26%), completely intrarenal (23%), pT1b (18%) and solitary kidney (7%). Data were prospectively collected and analyzed from an institutional review board approved database. RESULTS: Of 58 cases undergoing zero ischemia robotic (15) or laparoscopic (43) partial nephrectomy, 57 (98%) were completed without hilar clamping. Mean tumor size was 3.2 cm, mean ± SD R.E.N.A.L. score 7.0 ± 1.9, C-index 2.9 ± 2.4, operative time 4.4 hours, blood loss 206 cc and hospital stay 3.9 days. There were no intraoperative complications. Postoperative complications (22.8%) were low grade (Clavien grade 1 to 2) in 19.3% and high grade (Clavien grade 3 to 5) in 3.5%. All patients had negative cancer surgical margins (100%). Mean absolute and percent change in preoperative vs 4-month postoperative serum creatinine (0.2 mg/dl, 18%), estimated glomerular filtration rate (-11.4 ml/minute/1.73 m(2), 13%), and ipsilateral kidney function on radionuclide scanning at 6 months (-10%) correlated with mean percent kidney excised intraoperatively (18%). Although 21% of patients received a perioperative blood transfusion, no patient had acute or delayed renal hemorrhage, or lost a kidney. CONCLUSIONS: The concept of zero ischemia robotic and laparoscopic partial nephrectomy is presented. This anatomical vascular microdissection of the artery first and then tumor allows even complex tumors to be excised without hilar clamping. Global surgical renal ischemia is unnecessary for the majority of patients undergoing robotic and laparoscopic partial nephrectomy at our institution.

Current progress on augmented reality visualization in endoscopic surgery.

PURPOSE OF REVIEW: Advancements in surgery are progressing at a rapid rate; however, there are still limitations, including the ability to accurately visualize the target organ, in particular during laparoscopic surgery. Augmented reality visualization is a novel technique that has been developed to allow the fusion of three-dimensional medical images, such as those from transrectal ultrasound or computed tomography/MRI, with live camera images in real-time. In this review, we describe the current advancements and future directions of augmented reality and its application to laparoscopic surgery. RECENT FINDINGS: Geometrically-correct superimposed images can be generated by tracking of the laparoscope and registration of the target organ. The fused image between the live laparoscopic images and the reconstructed three-dimensional organ model aides the surgeon in his or her understanding of anatomical structures. Laparoscopic and robot-assisted surgeries in both general surgery and urology have been performed with technical success to date. The primary limitation of the current augmented reality systems is its infancy in dynamic tracking of organ motion or deformation. Recently, augmented reality systems with organ tracking based on real-time image analysis were developed. Further improvement and/or development of such new technologies would resolve these issues. SUMMARY: Augmented reality visualization is a significant advancement, improving the precision of laparoscopic/endoscopic surgery. New technologies to improve the dynamic tracking of organ motion or deformation are currently under investigation.

Anatomic renal artery branch microdissection to facilitate zero-ischemia partial nephrectomy.

BACKGROUND: Robot-assisted and laparoscopic partial nephrectomies (PNs) for medial tumors are technically challenging even with the hilum clamped and, until now, were impossible to perform with the hilum unclamped. OBJECTIVE: Evaluate whether targeted vascular microdissection (VMD) of renal artery branches allows zero-ischemia PN to be performed even for challenging medial tumors. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort evaluation of 44 patients with renal masses who underwent robot-assisted or laparoscopic zero-ischemia PN either with anatomic VMD (group 1; n=22) or without anatomic VMD (group 2; n=22) performed by a single surgeon from April 2010 to January 2011. INTERVENTION: Zero-ischemia PN with VMD incorporates four maneuvers: (1) preoperative computed tomographic reconstruction of renal arterial branch anatomy, (2) anatomic dissection of targeted, tumor-specific tertiary or higher-order renal arterial branches, (3) neurosurgical aneurysm microsurgical bulldog clamp(s) for superselective tumor devascularization, and (4) transient, controlled reduction of blood pressure, if necessary. MEASUREMENTS: Baseline, perioperative, and postoperative data were collected prospectively. RESULTS AND LIMITATIONS: Group 1 tumors were larger (4.3 vs 2.6 cm; p=0.011), were more often hilar (41% vs 9%; p=0.09), were medial (59% and 23%; p=0.017), were closer to the hilum (1.46 vs 3.26 cm; p=0.0002), and had a lower C index score (2.1 vs 3.9; p=0.004) and higher RENAL nephrometry scores (7.7 vs 6.2; p=0.013). Despite greater complexity, no group 1 tumor required hilar clamping, and perioperative outcomes were similar to those of group 2: operating room time (4.7 and 4.1h), median blood loss (200 and 100ml), surgical margins for cancer (all negative), major complications (0% and 9%), and minor complications (18% and 14%). The median serum creatinine level was similar 2 mo postoperatively (1.2 and 1.3mg/dl). The study was limited by the relatively small sample size. CONCLUSIONS: Anatomic targeted dissection and superselective control of tumor-specific renal arterial branches facilitate zero-ischemia PN. Even challenging medial and hilar tumors can be excised without hilar clamping. Global surgical renal ischemia has been eliminated for most patients undergoing PN at our institution.

Three-dimensional reconstruction of renovascular-tumor anatomy to facilitate zero-ischemia partial nephrectomy.

Zero-ischemia robotic and laparoscopic partial nephrectomy, a novel concept, eliminates ischemia to the tumor-free normal kidney. Anatomic microdissection of tertiary/higher-order tumor-specific arteries is performed to selectively devascularize only the tumor, maintaining normal perfusion of the remaining kidney. A thorough understanding of renovascular tumor anatomy is essential. Based on 0.5-mm-slice thickness computed tomography scans, we developed a novel three-dimensional (3D) reconstruction technique that fuses three key anatomic aspects: surface-rendered tumor, semitransparent kidney, and extra- and intrarenal arterial anatomy. Four central completely intrarenal hilar masses underwent 3D reconstruction for surgical navigation during zero-ischemia partial nephrectomy. Negative surgical margins were obtained in all four cases, with no intraoperative complications or transfusions. For these challenging laparoscopically invisible masses, 3D image navigation precisely identified tumor-specific arterial branches, thus facilitating zero-ischemia partial nephrectomy without hilar cross clamping.

Percutaneous radiofrequency ablation of virtual tumours in canine kidney using Global Positioning System-like technology.

UNLABELLED: What's known on the subject? And what does the study add? We have previously shown that percutaneous radiofrequency ablation guided by image-fusion technology allows for precise needle placement with real time ultrasound superimposed with pre-loaded imaging, removing the need for real-time CT or MR guidance. Emerging technology also allows real-time tracking of a treatment needle within an organ in a virtually created 3D format. To our knowledge, this is the first study utilising a sophisticated ultrasound-based navigation system that uses both image-fusion and real-time probe-tracking technologies for in-vivo renal ablative intervention. OBJECTIVES: • To evaluate the feasibility, accuracy and efficacy of ultrasonography (US)-guided percutaneous radiofrequency ablation (RFA) in the canine kidney model using novel Global Positioning System-like probe tracking technology. • Virtual tumours in the canine kidney were ablated in vivo by percutaneous RFA guided exclusively by two-dimensional (2D) US and a virtual navigation system. MATERIALS AND METHODS: • Gold fiducial markers were inserted into renal parenchyma to serve as centres of virtual tumours. • After capturing 2D US images, navigation software created a three-dimensional planning model of the kidney, and superimposed it onto the live US image. • Percutaneous RFA was guided by multiplanar navigation, showing real-time probe positions within the superimposed images, to treat each virtual tumour with a single treatment. • Navigator software predicted the percentage of tumour treated; treated kidney specimens were examined to evaluate projection and targeting accuracy. RESULTS: • In total, 32 virtual tumours (median diameter 16 mm, range 10-24 mm) were treated in 16 canine kidneys. • Median (range) error between 'fiducial tumour centre' and 'treated area centre' was 1.8 (0-25) mm. • Targeting accuracy improved with experience: median (range) error decreased from 6.3 (2-25) mm in an initial 12 tumours to 1.3 (0-9.0) mm in the last 20 tumours (P= 0.008). • The percentage (range) of tumour actually treated improved significantly from the initial series at 23% (0-100%) to 100% (51-100%) (P < 0.001). • Overall, navigator-reported and pathologically confirmed treatment percentages were correlated significantly (r= 0.5; P= 0.006). CONCLUSIONS: • Percutaneous renal RFA guided exclusively by real-time 2D US with multiplanar Global Positioning System-like probe tracking is feasible and accurate. • Near-future technologies, including elastic fusion overlay and anticipation of soft-tissue deformation, will further augment this guidance system.

Expertise modeling for automated planning of acetabular cup in total hip arthroplasty using combined bone and implant statistical atlases.

Intraoperative robotic and computer-guided assistances are now commonly used in total hip arthroplasty (THA) for accurate execution of the preoperative plan. Although the preoperative plan to be accurately executed is critical, it is still interactively prepared in a time-consuming and subjective manner. In this paper, atlas-based approach to automated surgical planning of the acetabular cup in THA is described to stabilize its quality as well as reduce its time-consuming nature. Surgeon's expertise is embedded in two types of statistical atlases, which are constructed from training datasets of CT-based 3D plans prepared by experienced surgeons. One is a statistical shape model which encodes global spatial relationships between the patient anatomy and implant. The other is the statistical map of residual bone thickness on the implant surface, which encodes local spatial constraints of the anatomy and implant. Given the 3D pelvis shape of the patient, we formulate a procedure to determine the best size and position of the acetabular cup which satisfy the constraints derived from the two statistical atlases. We validated the proposed planning method by retrospective study using the datasets which were actually used in the THA surgery.

Construction of a statistical surgical plan atlas for automated 3D planning of femoral component in total hip arthroplasty.

The problem of automating preoperative planning of the femoral component (stem) for total hip arthroplasty (THA) is addressed. In our previous method, time-consuming trial-and-error processes were involved in parameter tuning of the objective function. This problem prevents application in different stem systems. To overcome this problem, a statistical surgical plan atlas (SSPA) is constructed from training datasets of stem planning. The SSPA represents the average and variance of the distance distribution on the stem surface to the femoral canal surface. That is, it encodes the distribution of the degree of contact preferred by the surgeon. Automated planning is performed by minimizing the squared difference between distributions of the SSPA and planning solution. The proposed method involves no parameter tuning to define the objective function that evaluates differences from the planning the surgeon prefers. Experimental evaluations showed that the proposed method renders parameter tuning unnecessary while it still provides comparable accuracy to the previous method.

Intraoperative magnetic tracker calibration using a magneto-optic hybrid tracker for 3-D ultrasound-based navigation in laparoscopic surgery.

This paper describes a ultrasound (3-D US) system that aims to achieve augmented reality (AR) visualization during laparoscopic surgery, especially for the liver. To acquire 3-D US data of the liver, the tip of a laparoscopic ultrasound probe is tracked inside the abdominal cavity using a magnetic tracker. The accuracy of magnetic trackers, however, is greatly affected by magnetic field distortion that results from the close proximity of metal objects and electronic equipment, which is usually unavoidable in the operating room. In this paper, we describe a calibration method for intraoperative magnetic distortion that can be applied to laparoscopic 3-D US data acquisition; we evaluate the accuracy and feasibility of the method by in vitro and in vivo experiments. Although calibration data can be acquired freehand using a magneto-optic hybrid tracker, there are two problems associated with this method--error caused by the time delay between measurements of the optical and magnetic trackers, and instability of the calibration accuracy that results from the uniformity and density of calibration data. A temporal calibration procedure is developed to estimate the time delay, which is then integrated into the calibration, and a distortion model is formulated by zeroth-degree to fourth-degree polynomial fitting to the calibration data. In the in vivo experiment using a pig, the positional error caused by magnetic distortion was reduced from 44.1 to 2.9 mm. The standard deviation of corrected target positions was less than 1.0 mm. Freehand acquisition of calibration data was performed smoothly using a magneto-optic hybrid sampling tool through a trocar under guidance by realtime 3-D monitoring of the tool trajectory; data acquisition time was less than 2 min. The present study suggests that our proposed method could correct for magnetic field distortion inside the patient's abdomen during a laparoscopic procedure within a clinically permissible period of time, as well as enabling an accurate 3-D US reconstruction to be obtained that can be superimposed onto live endoscopic images.

Thoracoscopic surgical navigation system for cancer localization in collapsed lung based on estimation of lung deformation.

We have developed a thoracoscopic surgical navigation system for lung cancer localization. In our system, the thoracic cage and mediastinum are localized using rigid registration between the intraoperatively digitized surface points and the preoperative CT surface model, and then the lung deformation field is estimated using nonrigid registration between the registered and digitized point datasets on the collapsed lung surface and the preoperative CT lung surface model to predict cancer locations. In this paper, improved methods on key components of the system are investigated to realize clinically acceptable usability and accuracy. Firstly, we implement a non-contact surface digitizer under thoracoscopic control using an optically tracked laser pointer. Secondly, we establish a rigid registration protocol which minimizes the influence of the deformation in different patient's positions by analyzing MR images of volunteers. These techniques were evaluated by in vitro and clinical experiments.